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Brain imaging combined with artificial intelligence has identified six distinct "biotypes" of depression and anxiety that may lead to more personalized and effective treatment. This research has "immediate clinical implications," study investigator Leanne Williams, PhD, director of the Stanford Medicine Center for Precision Mental Health and Wellness, told Medscape Medical News. "At Stanford, we have started translating the imaging technology into use in a new precision mental health clinic. The technology is being actively developed for wider use in clinical settings, and we hope to make it accessible to more clinicians and patients," Williams said. The study was published online on June 17, 2024, in Nature Medicine. No More Trial and Error? Depression is a highly heterogeneous disease, with individual patients having different symptoms and treatment responses. About 30% of patients with major depression are resistant to treatment, and about half of patients with generalized anxiety disorder do not respond to first-line treatment. "The dominant 'one-size-fits-all' diagnostic approach in psychiatry leads to cycling through treatment options by trial and error, which is lengthy, expensive, and frustrating, with 30-40% of patients not achieving remission after trying one treatment," the authors noted. "The goal of our work is figuring out how we can get it right the first time," Williams said in a news release, and that requires a better understanding of the neurobiology of depression. To that end, 801 adults diagnosed with depression and anxiety underwent functional MRI to measure brain activity at rest and when engaged in tasks designed to test cognitive and emotional functioning. Researchers probed six brain circuits previously associated with depression: The default mode circuit, salience circuit, attention circuit, negative affect circuit, positive affect circuit, and the cognitive control circuit. Using a machine learning technique known as cluster analysis to group the patients' brain images, they identified six clinically distinct biotypes of depression and anxiety defined by specific profiles of dysfunction within both task-free and task-evoked brain circuits. "Importantly for clinical translation, these biotypes predict response to different pharmacological and behavioral interventions," investigators wrote. For example, patients with a biotype characterized by overactivity in cognitive regions of the brain experienced the best response to the antidepressant venlafaxine compared with patients with other biotypes. Patients with a different biotype, characterized by higher at-rest levels of activity in three regions associated with depression and problem-solving, responded better to behavioral therapy. In addition, those with a third biotype, who had lower levels of activity at rest in the brain circuit that controls attention, were less apt to see improvement of their symptoms with behavioral therapy than those with other biotypes. The various biotypes also correlated with differences in symptoms and task performance. For example, individuals with overactive cognitive regions of the brain had higher levels of anhedonia than those with other biotypes, and they also performed worse on tasks measuring executive function. Those with the biotype that responded best to behavioral therapy also made errors on executive function tasks but performed well on cognitive tasks. A Work in Progress The findings provide a deeper understanding of the neurobiological underpinnings of depression and anxiety and could lead to improved diagnostic accuracy and more tailored treatment approaches, the researchers noted. Naming the biotypes is a work in progress, Williams said. "We have thought a lot about the naming. In the Nature Medicine paper, we use a technical convention to name the biotypes based on which brain circuit problems define each of them," she explained. "For example, the first biotype is called DC+SC+AC+ because it is defined by connectivity increases [C+] on three resting circuits — default mode [D], salience [S], and frontoparietal attention [A]. We are working with collaborators to generate biotype names that could be convergent across findings and labs. In the near future, we anticipate generating more descriptive medical names that clinicians could refer to alongside the technical names," Williams said. Commenting on the research for Medscape Medical News, James Murrough, MD, PhD, director of the Depression and Anxiety Center for Research and Treatment at the Icahn School of Medicine at Mount Sinai, New York City, called it "super exciting." "The work from this research group is an excellent example of where precision psychiatry research is right now, particularly with regard to the use of brain imaging to personalize treatment, and this paper gives us a glimpse of where we could be in the not-too-distant future," Murrough said. However, he cautioned that at this point, "we're far from realizing the dream of precision psychiatry. We just don't have robust evidence that brain imaging markers can really guide clinical decision making currently." Note: This article originally appeared on Medscape.

A history of traumatic brain injury (TBI) is associated with a 33% increased risk for schizophrenia and a 78% increase in bipolar disorder (BD), with the strongest link in older adults, women, and those with severe TBI, new research suggested. "Findings indicate that TBI is a risk factor for both schizophrenia and [BD] with differential impact by age, severity, and sex, and that this association cannot be explained by familial confounding alone," investigators led by Kai-Yuan Cheng, MD, PhD, of the Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden, wrote. "The associations between TBI with schizophrenia and [BD] risks call on clinicians to monitor clinical course and potential psychiatric symptoms in people with a history of TBI, particularly the vulnerable groups identified in our study," they added. The study was published online on June 2, 2024, in Psychiatry Research. Conflicting Findings TBI is associated with elevated risk for several psychiatric conditions, including depression, anxiety, posttraumatic stress disorder, and suicidality, but evidence linking TBI to the risk for schizophrenia and BD has been based largely on small studies and yielded conflicting results. The researchers identified 4184 individuals with schizophrenia and 18,681 with BD from Swedish national registries. Patients were aged ≥ 15 years at first diagnosis and born between 1973 and 1998. Controls included 20,920 controls with schizophrenia and 93,405 patients with BD who were matched with controls by birth year, sex, and birthplace. They also matched cases with siblings who had neither disorder. Those with schizophrenia were predominantly men (66% in the case-control group and 57% in the sibling group), while women predominated in the BD samples (66% in case-controls and 56% in the sibling group). Within all samples, the proportion of individuals who had experienced TBI was consistently higher among cases vs control individuals. In the nested case-control samples, experiencing any TBI was associated with a significantly higher risk for schizophrenia (incidence rate ratio [IRR], 1.33) and BD (IRR, 1.78; both P < .001). Moderate and severe TBI vs mild TBI were associated with higher relative risk for schizophrenia and BD, and later age vs earlier age at first TBI (≥ 15 years) was associated with a higher risk for both conditions. "A dose-response relationship is an important element in establishing a causal relationship as it yields evidence of potential biological plausibility and gradient," the researchers wrote. The sibling comparison samples, designed to adjust for familiar confounding, yielded hazard ratios (HRs) that complemented findings, with TBI remaining significantly associated both with schizophrenia and BD (adjusted HR [aHR], 1.38; P = .002 and aHR, 1.55; P < .001, respectively). Severity and later age of TBI were also associated with stronger risks for both conditions. The association between TBI and BD was significantly stronger in women vs men, which applied to any TBI exposure and TBI sustained at different ages. However, the pattern of excess risk for women in schizophrenia was not statistically significant. Limitations included the fact that primary care diagnoses were not included in the data, and outpatient diagnoses were only recorded from 2001 — which may have led to missing milder TBI exposures and some outcome diagnoses. In addition, data on family design were not comprehensive, and siblings born at different times may not have grown up in the same environment. Lastly, it was not possible to completely rule out the potential biases of residual confounding effects — especially reverse causality. The researchers suggested the findings underscore the need for further research establishing a "clear pathophysiological mechanism" between TBI and severe mental illness. Note: This article originally appeared on Medscape.

Keypoint: Do physical health conditions in childhood affect ADHD symptoms at age 17 years? Researchers investigated these associations in a large cohort study. CASE VIGNETTE “Kate” is a 17-year-old Caucasian female with a history of attention-deficit/hyperactivity disorder (ADHD), diagnosed at age 10 years. She presented with primarily inattentive symptoms and minimal issues with hyperactivity or impulsivity. She has a history of myopia and has worn eyeglasses since age 13 years. She was also diagnosed with asthma at age 6 years. Her body mass index is in the 40th percentile. Kate had a positive response to treatment with methylphenidate, which she continues to take, although she is still sometimes easily distracted. At an outpatient visit, her mother asks whether Kate’s asthma could impact on her ADHD symptoms. As Kate’s psychiatrist, how would you respond? Increasing evidence suggests that ADHD is associated with physical comorbidities, including asthma and obesity.1 A recent birth cohort study found cross-sectional associations between ADHD symptoms, asthma, and sleep problems in early and middle childhood and adolescence.2 There may be a bidirectional association between ADHD and physical conditions, as well as common underlying risk factors.3 Few studies have investigated longitudinal associations between ADHD and physical conditions. The Current Study Reed and colleagues4 used a large-scale population-representative sample to investigate the hypothesis that the cumulative number of physical health conditions across childhood are associated with ADHD symptoms in adolescence (age 17 years), controlling for cumulative environmental risk, ADHD medications, and ADHD symptoms at age 3 years. The authors used data from the Millennium Cohort Study, which contains longitudinal data on > 19,000 UK families with children born between 2000 and 2002. Data have been collected in 7 waves, at ages 9 months and 3, 5, 7, 11, 14, and 17 years. Only the first sibling in each family was included. Participants were also excluded if data on the biological mother was unavailable, if physical health predictor variables were missing, or if outcome data at age 17 years was missing. The present study included 8059 participants. The parent-reported hyperactivity/inattention subscale of the Strengths and Difficulties Questionnaire (SDQ), which predicts ADHD diagnosis,5 was collected at age 17 years, and SDQ score at age 3 years was also included as a potential confounding factor. Approximately 174 children in the cohort were diagnosed with ADHD by age 17 years. Parents were asked about their child’s physical health at each wave, including diagnoses and hospitalizations. Physical conditions were grouped into 4 clusters: Sensory (eyesight, hearing) Atopic (eczema, asthma, hay fever) Neurological (epilepsy, sleep problems, movement problems, stutter) Cardiometabolic (obesity, diabetes, heart problems) Risk factors were grouped into 5 cumulative risk indices: Prenatal Perinatal Postnatal environment Postnatal maternal well-being Socioeconomic status and demographics At age 14 years, data on ADHD medications were also obtained. Data were analyzed using stepwise multiple linear regression to analyze the relationship between physical health clusters and ADHD symptoms at age 17 years, controlling for environmental risk indices, ADHD medications, and SDQ score at age 3 years. Binary logistic regression models were also used with ADHD diagnosis as the outcome. Approximately 91 children were taking ADHD medication, and the average SDQ score at age 17 years was 2.6. After adjusting for confounders, sensory and neurological clusters were significantly associated with ADHD symptoms as a continuous measure at age 17 years (β=0.06 for each), and the model explained 21% of the variance. In binary logistic regression analyses, both the sensory cluster (OR=1.31, 95% CI 1.04-1.65) and the neurological cluster (OR=1.94, 95% CI 1.48-2.53) predicted ADHD diagnosis. The odds of an ADHD diagnosis approximately doubled with each additional neurological condition. Study Conclusions The investigators concluded that this was the first study to analyze the longitudinal association between physical conditions in childhood and ADHD symptoms. Sensory and neurological clusters, but not the atopic or cardiometabolic clusters, were significant predictors of hyperactivity/inattention symptoms at age 17 years. Participants with predating neurological issues were almost 2 times more likely to have an ADHD diagnosis at age 17 years. Study strengths included the large cumulative sample size, the availability of longitudinal data, and consideration of potential confounding effects of environmental risk factors and ADHD medications. Limitations include that the SDQ is not designed as a screening instrument for ADHD, and only a small subset of participants had been clinically evaluated for ADHD. The investigators did not explore ADHD symptoms as predictors of physical health (the reverse relationship). Data were not available to analyze the effect of parental history of ADHD on these associations. The Bottom Line Findings suggest possible biological commonalities between physical disorders in childhood and ADHD symptoms in adolescence. Clinicians should monitor for symptoms of hyperactivity and inattention in children with sensory and neurological disorders. Note: This article originally appeared on Psychiatric Times

Gray matter volume, BDNF and cytokine levels, and depressive symptoms partially mediate the cognitive decline associated with loneliness. Risk Factors for Cognitive Decline Loneliness contributes to both psychological risk factors for cognitive decline and structural brain changes that are linked to dementia, according to study results published in Brain Behavior and Immunity. Given that older adults are more susceptible to loneliness, targeted interventions for this vulnerable population are needed to prevent adverse health impacts. Previous research has established a relationship between loneliness and poorer mental and physical health outcomes, particularly among older adults. However, few studies have examined the neurobiological mechanisms underlying loneliness in adults aged 65 and older, and how these changes may impact cognitive function. To investigate this further, researchers used data from the Rush Memory and Aging Project (RMAP) determine whether the psychobiological conditions of loneliness increase the risk for cognitive decline among adults aged 65 and older. To measure loneliness, participants completed a modified version of the de Jong-Gierveld Loneliness Scale. The researchers assessed 5 cognitive domains: episodic memory, semantic memory, working memory, visuospatial ability, and processing speed. Additionally, the researchers examined levels of proinflammatory cytokines and brain-derived neurotrophic factor (BDNF), depressive symptoms, and total gray matter volume as potential contributing factors to the relationship between loneliness and cognition. A total of 2130 participants had complete data for loneliness, depressive symptoms, and cognitive measures. Among these participants, 73% were women, 93% were White, 5% were Hispanic, and they were 80.1 years of age, on average. However, the sample size was reduced for the analyses that evaluated cytokines (n=414-423), BDNF (n=272), and gray matter volume (n=664). The researchers found that loneliness was negatively associated with episodic memory (β= -0.1; SE, 0.01; t = -73; P <.001), semantic memory (β= -0.06; SE, 0.01; t = -5.9; P <.001), working memory (β= -0.06; SE, 0.00; t = -5.9; P <.001), visuospatial ability (β= -0.07; SE, 0.01; t = -7.25; P <.001), processing speed (β= -0.08; SE, 0.01; t = -3.86; P <.001), and global cognition (β= -0.06; SE, 0.01; t = -8.32; P <.001). The researchers then evaluated potential pathophysiological pathways that may explain the relationship between loneliness and cognition. The researchers observed a significant, positive correlation between BDNF levels and all cognitive domains (all P <.001). When BDNF was added to the linear mixed model, there was a 3-way interaction between BDNF, time, and loneliness (β=0.05; SE, 0.02; P <.05) and a likelihood ratio test indicated that adding BDNF to the model significantly improved the model’s prediction (χ2=6.59; P =.01). Similarly, the researchers observed a 3-way interaction between cytokine levels, time, and loneliness (β= -0.12; SE, 0.05; P <.05) Total gray matter volume was also a significant mediator of the relationship between cognition and loneliness, with the exception of working memory, accounting for 15% to 25% of the observed relationship. Further, depressive symptoms were a mediating factor for all cognitive domains except visuospatial ability. The mediating effect of depressive symptoms explained 12% of the relationship between loneliness and episodic memory, 17% of processing speed, 41% of visuospatial ability, and 15% of global memory. Study authors concluded, “As demonstrated in this study, loneliness is related not only to psychological risk factors of cognitive decline, such as depression but also to structural changes in the brain that are significant predictors of dementia.” Study limitations include the fact that the observed significant associations between longitudinal scores of loneliness and cognitive decline had a small effect size, the sample size was smaller for participants with neuroimaging and measures of loneliness and depressive symptoms, and most MAP participants were White. Note: This article originally appeared on Psychiatry Advisor

Adults with posttraumatic stress disorder (PTSD) have smaller cerebellums than unaffected adults, suggesting that this part of the brain may be a potential therapeutic target. According to recent research on more than 4000 adults, cerebellum volume was significantly smaller (by about 2%) in those with PTSD than in trauma-exposed and trauma-naive controls without PTSD. "The differences were largely within the posterior lobe, where a lot of the more cognitive functions attributed to the cerebellum seem to localize, as well as the vermis, which is linked to a lot of emotional processing functions," lead author Ashley Huggins, PhD, said in a news release. "If we know what areas are implicated, then we can start to focus interventions like brain stimulation on the cerebellum and potentially improve treatment outcomes," said Huggins, who worked on the study while a postdoctoral researcher in the lab of Rajendra Morey, MD, at Duke University, Durham, North Carolina, and is now at the University of Arizona, Tucson. While the cerebellum is known for its role in coordinating movement and balance, it also plays a key role in emotions and memory, which are affected by PTSD. Smaller cerebellar volume has been observed in some adult and pediatric populations with PTSD. However, those studies have been limited by either small sample sizes, the failure to consider key neuroanatomical subdivisions of the cerebellum, or a focus on certain populations such as veterans of sexual assault victims with PTSD. To overcome these limitations, the researchers conducted a mega-analysis of total and subregional cerebellar volumes in a large, multicohort dataset from the Enhancing NeuroImaging Genetics through Meta-Analysis (ENIGMA)-Psychiatric Genomics Consortium PTSD workgroup that was published online on January 10, 2024, in Molecular Psychiatry. They employed a novel, standardized ENIGMA cerebellum parcellation protocol to quantify cerebellar lobule volumes using structural MRI data from 1642 adults with PTSD and 2573 healthy controls without PTSD (88% trauma-exposed and 12% trauma-naive). After adjusting for age, gender, and total intracranial volume, PTSD was associated with significant gray and white matter reductions of the cerebellum. People with PTSD demonstrated smaller total cerebellum volume as well as reduced volume in subregions primarily within the posterior cerebellum, vermis, and flocculonodular cerebellum than controls. In general, PTSD severity was more robustly associated with cerebellar volume differences than PTSD diagnosis. Focusing purely on a "yes-or-no" categorical diagnosis didn't always provide the clearest picture. "When we looked at PTSD severity, people who had more severe forms of the disorder had an even smaller cerebellar volume," Huggins explained in the news release. Novel Treatment Target PTSD These findings add to "an emerging literature that underscores the relevance of cerebellar structure in the pathophysiology of PTSD," the researchers noted. They caution that despite the significant findings suggesting associations between PTSD and smaller cerebellar volumes, effect sizes were small. "As such, it is unlikely that structural cerebellar volumes alone will provide a clinically useful biomarker (eg, for individual-level prediction)." Nonetheless, the study highlights the cerebellum as a "novel treatment target that may be leveraged to improve treatment outcomes for PTSD," they wrote. They noted that prior work has shown that the cerebellum is sensitive to external modulation. For example, noninvasive brain stimulation of the cerebellum has been shown to modulate cognitive, emotional, and social processes commonly disrupted in PTSD. Commenting on this research for Medscape Medical News, Cyrus A. Raji, MD, PhD, associate professor of radiology and neurology at Washington University in St. Louis, Saint Louis, Missouri, noted that this "large neuroimaging study links PTSD to cerebellar volume loss." "However, PTSD and traumatic brain injury frequently co-occur, and PTSD also frequently arises after TBI. Additionally, TBI is strongly linked to cerebellar volume loss," Raji pointed out. "Future studies need to better delineate volume loss from these conditions, especially when they are comorbid, though the expectation is these effects would be additive with TBI being the initial and most severe driving force," Raji added. The research had no commercial funding. Author disclosures are listed with the original article. Raji is a consultant for Brainreader, Apollo Health, Pacific Neuroscience Foundation, and Neurevolution Medicine LLC. This article originally appeared on Medscape

Prevention-based interventions are effective in increasing cannabis risk perception and reducing cannabis use among adolescents. Increased knowledge and a greater perception of cannabis risk in adolescents are associated with decreased current usage and reduced intentions for future use, according to study results published in the Journal of Adolescent Health. While prevention-based interventions were generally effective in enhancing knowledge and perception of cannabis risk, legislative changes demonstrate considerable heterogeneity in outcomes. Cannabis remains the predominantly used illicit substance by adolescents on a global scale, and given recent legislative changes to cannabis legalization, investigators aimed to establish a comprehensive understanding of adolescents’ general knowledge and perception of risk for cannabis and whether legislation impacted these variables. The investigators conducted a systematic literature review by searching publication databases from inception to February 2022 for articles that reported on cannabis knowledge and its risk perception among children and adolescents (10 to 18 years of age). Levels of evidence for each study included were determined using the Center for Evidence Based Medicine’s framework, with Level 1A (systematic review of randomized controlled trials) representing the highest level of evidence and Level 5 (expert opinion, physiology bench research, or “first principles”) being the lowest. A total of 133 articles were included in the final analysis. Most studies (n=93) were categorized as evidence grade level 2C, involving outcome studies from large database registries and population-based data, while 22% (n=30) met the criteria for level 2B studies, which includes cohort studies and lower-quality RCTs. Over 90% of the studies were conducted in high-income countries (eg, United States, Canada, Australia, England, France), with limited representation from upper and lower middle-income countries. Overall, increased awareness and knowledge regarding the perceived risk for cannabis among adolescents was frequently associated with reduced current usage and future use intentions of cannabis. Studies investigating associations over time demonstrated a rise in adolescent cannabis use alongside a decline in risk perception. However, the investigators observed that prevention interventions frequently improved knowledge and risk perception among these adolescents. For example, a Psychostimulant and Cannabis Module led to significantly higher levels of cannabis-related knowledge in intervention groups compared with controls, even at 10 months post-intervention (P <.001). Additionally, a life-skills training program with a drug education unit for middle school students resulted in reduced lifetime (P =.05) and recent (P <.03) marijuana use 2 years after intervention, relative to controls. In contrast, legislative changes led to heterogeneous knowledge and risk perception outcomes. Medicinal marijuana legislation consistently demonstrated a reduction in risk perception among adolescents, while studies that evaluated recreational marijuana legislation observed significant variability in both knowledge and use outcomes. Notably, studies that assessed adolescents’ knowledge and perception of risks associated with cannabis use as a primary outcome revealed that a lack of comprehensive understanding regarding the health implications of marijuana usage was consistently associated with higher rates of current usage and intentions for future use. Review authors concluded, “[T]argeted public health strategies that seek to increase cannabis-related knowledge among youth and disseminate information about the potential health harms of cannabis use should continue and be prioritized as a means of protecting youth and mitigating rates of cannabis use in adolescents.” The findings of this review may be limited by the inclusion of manuscripts exclusively published in English, and the high risk for bias found in 95% of included studies. This article originally appeared on Psychiatry Advisor

Heavy secondhand smoke exposure was positively associated with a higher risk of developing severe headaches or migraine in adults who never smoked. Among adults who never smoke, heavy secondhand smoke exposure is positively associated with severe headaches or migraine, according to study findings published in the journal Headache. To determine if an association exists between secondhand smoke exposure and severe headaches or migraine, validated by serum cotinine levels, among adults who never smoked, researchers conducted a cross-sectional study and collected data via the 1999-2004 National Health and Nutrition Examination Survey (NHANES). Serum cotinine levels exceeding 10 ng/mL were frequently observed in current smokers, establishing a threshold value. To be classified as nonsmoker, individuals must have smoked fewer than 100 cigarettes in their lifetime, abstained from nicotine-containing products for the past 5 days, and had serum cotinine levels of 10 ng/mL or less. The researchers determined migraine headache status by asking participants whether they have experienced severe headaches or migraine during the previous 3 months. After excluding participants, a total of 4560 individuals (median age, 43; female 60.1%; 71.5% White) who had completed the NHANES survey were included in the final analysis. Among participants, 919 (20%) self-reported experiencing severe headaches or migraine. After accounting for relevant covariates, the researchers observed a significant association between high levels of secondhand smoke exposure and an increased risk for severe headaches or migraine (odds ratio [OR], 2.02; 95% CI, 1.19-3.43). In contrast, low secondhand smoke exposure demonstrated no significant association with severe headaches or migraine (OR, 1.15; 95% CI, 0.91-1.47). When compared with individuals with no secondhand smoke exposure, those with a body mass index (BMI) less than 25 and those who were sedentary (P =.016) showed a significant association with both low secondhand smoke exposure (OR, 2.15; 95% CI, 1.54-2.99) and heavy secondhand smoke exposure (OR, 2.60, 95% CI; 1.25-5.42) and severe headache or migraine. Among individuals with a BMI of 25–30, no significant association was found between low secondhand smoke exposure (OR, 0.77; 95% CI, 0.51-1.15) or heavy secondhand smoke exposure (OR, 1.14; 95% CI, 0.47-2.76). The results indicated a distinct linear association between the natural logarithm of serum cotinine and the occurrence of severe headaches or migraine (P =.335 for nonlinearity). In sensitivity analyses, which excluded active smokers with serum cotinine concentrations more than 3 ng/mL, participants on specific medications, and after multiple imputations, the association persisted with a slight decrease in the odds ratio value. The study has several limitations including the inability to establish a causal relationship between secondhand smoke exposure and severe headache or migraine. Moreover, the half-life of serum cotinine is 15-40 hours, which can only reveal recent secondhand smoke exposure. “These findings underscore the harmful impact of [secondhand smoke] exposure on the nervous system and serve as a reminder to avoid prolonged exposure to tobacco smoke,” the researchers concluded. This article originally appeared on Neurology Advisor

Jordan Peterson Shares How To HEAL From Emotional Trauma Great video about dealing from emotional trauma

The similarities in clinical phenotypes between PBD and ADHD may be caused by decreased gray matter volumes in the insula and anterior cingulate cortex seen in both conditions. Pediatric bipolar disorder (PBD) and attention-deficit/hyperactivity disorder (ADHD) were found to have both shared and distinct alterations in gray matter volumes (GMVs). These findings from a systematic review and meta-analysis were published in the Journal of the American Academy of Child & Adolescent Psychiatry. Among children, PBD and ADHD frequently co-occur and can affect similar cognitive and affective functions. However, both conditions also have unique, non-overlapping characteristics (eg, PBD typically affects executive functioning whereas ADHD affects attention and working memory). To compare the underlying neurobiological bases of these 2 conditions, investigators searched publication databases from inception through January 2022 for neuroimaging studies that compared PBD or ADHD groups to healthy controls in order to identify common and distinct neural substrates. A total of 42 articles were included for analysis, of which 32 assessed ADHD and 10 investigated PBD. The pooled sample size comprised 1333 cases with ADHD and 1308 controls and 268 cases with PBD and 385 controls, respectively. The patient groups with PBD and ADHD comprised 51% and 21% girls (P <.001) and they were 16.2 and 12.8 years of age (P <.001) on average, respectively. The control groups for both conditions were age- and gender-matched with cases. The investigators found shared GMV changes among the ADHD and PBD groups, with decreased volumes in the right insula (peak coordinates: 50, -4, 0; z=1.615; cluster size=100) and right anterior cingulate cortex (peak coordinates: 2, 26, -14; z=1.683; cluster size=22). These areas correspond with the functions of emotion processing and attention, respectively. In comparing PBD and ADHD cases, the PBD group had smaller GMVs than cases with ADHD in the right inferior frontal gyrus (peak coordinates: 52, 20, 26; z=1.682; cluster size=835), left orbitofrontal cortex (peak coordinates: 0, 24, -26; z=1.664; cluster size=261), and left hippocampus (peak coordinates: -20, -14, -10; z=1.517; cluster size=188). Conversely, cases with ADHD had greater GMV decreases than cases with PBD in the left precentral gyrus (peak coordinates: -40, -8, 56; z= -2.017; cluster size=158), left inferior frontal gyrus (peak coordinates: -26, 16, -24; z= -2.081; cluster size=59), and right superior frontal gyrus (peak coordinates: 26, 68, 0; z= -1.950; cluster size=28). When compared with controls, PBD cases had reduced GMVs in the left orbitofrontal cortex, left amygdala, and right inferior frontal gyrus. Cases with PBD had larger GMV in the left hippocampus associated with increasing age (R2, 0.276; P <.001) and boys had greater GMV abnormalities in the left hippocampus relative to girls. Cases with ADHD had decreased GMVs in the right anterior cingulate cortex, right insula, left precentral gyrus, and left inferior frontal gyrus and increased GMV in the bilateral thalamus relative to controls. Smaller GMV in the left inferior frontal gyrus was observed with increasing age among cases relative to controls (R2, 0.392; P <.001). Study authors concluded, “Overlapping anatomic substrates may account for similarities in the clinical presentation of PBD and ADHD, while disorder-differentiating regional alterations may account for the greater affective disturbances in PBD and greater neurocognitive and motor function disturbances in ADHD.” These study findings may be limited by the use of peak coordinate data instead of raw brain map data. Disclosure: Multiple study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures. This article originally appeared on Psychiatry Advisor

A "global human energy crisis" is coming. How can emotional intelligence help us navigate it? Are you and your team burned out? Increased rates of burnout impact the well-being of providers and the quality of care for patients. In a recent study, the American Medical Association reports half of physicians now experience aspects of burnout. Research at Six Seconds shows we are headed to a “global human energy crisis” with far-reaching implications for the entire health care system. What can disrupt burnout? Primary care physicians and other clinicians and health care providers can develop measurable skills of emotional intelligence to improve their well-being and workplace performance. Mental Health is a Workplace Issue Frontline health care workers were some of the hardest hit by the pandemic. In addition to tremendous workload, the added mental health effects of fear and uncertainty depleted people and the consequences of prolonged stress on the system have arrived. As World Health Organization Director General Tedros Adhanom Ghebreyesus said in March 2021, the pandemic has a long-term emotional impact: “When there is mass trauma, it affects communities for many years to come.” The effects of burnout are both personal and professional. In health care, emotional depletion is linked to higher turnover, more absenteeism, more errors and accidents, and an increase in unhealthy coping strategies (such as substance abuse). Mind Share Partners’ Mental Health at Work Report shows massive increases in mental health burdens at work, with 84% of respondents stating work has a negative effect on their mental health. The Workforce Institute at UKG found people’s supervisors had as much mental health impact as a spouse – and more than a therapist. Whether you’re in a formal role of leader, such as a private practice or supervising others in a hospital, you hold a position of leadership. In that position, your choices, your role-modeling, your interactions have a direct impact on others’ mental health and well-being. A Surprising Myth: Burnout is Not About Overwork Burnout is the feeling of being utterly depleted, unmotivated and detached from one’s work. As defined by the World Health Organization, burnout is: Physical and emotional exhaustion Depersonalization / detachment / cynicism Decline in sense of personal accomplishment Burnout’s causes are deeply linked to basic emotional needs like belonging, purpose, recognition and autonomy. Research backs this up. In a recent JAMA Network Open original investigation, physician burnout is connected to professional fulfillment. This study ranked at the most burned out and disconnected physicians by specialty. The results may surprise you (Figure 1). Do You Recognize Burnout? In this model (Figure 2) adapted from Freundenberger’s development of burnout research, we can see how burnout behaviors build and reinforce a cycle of overwork, degraded relationships and mental health issues. What are the key causes of burnout? Research has identified the following four factors: A perceived lack of control or autonomy Insufficient reward or recognition A perceived lack of social support / community A perceived lack of meaning / purpose While the burnout numbers are alarming, they should be a call to action: Clinicians and staff members are adversely affected by the increased emotional turmoil, and to meet this challenge, new skills are required. Emotional Intelligence for Health Care Providers Emotional intelligence has a mitigating effect on burnout for health care workers. In a 2022 cross-sectional public health study, researchers found “improving the emotional intelligence of health care staff has practical significance in reducing the level of job burnout directly and will reduce the incidence of burnout by reducing the frequency of violence (especially for emotional exhaustion and depersonalization).” How does emotional intelligence support health care professionals? We spoke with Carlos A. Pellegrini MD, FACS, executive coach, former chief medical officer of UW Medicine, and current chair of the Joint Commission. He points out that emotional intelligence is integral to a physician’s work: “The practice of medicine today requires clear, constant, and concise communications with the patients and with all other care providers.This starts with introspection – knowing and understanding our own emotions. That in turn, allows us to choose how we interact with them, to share and to give ourselves, and that elicits a need for all others to “give” (knowledge, skills, expertise) and share their emotions with us.The pursuit of excellence in medicine is tied to the emotional intelligence of the provider.” Five Ways to Reverse Burnout in Your Workplace The link between mental health and work led the U.S. Surgeon General, Vice Admiral Vivek Murthy, MD, MBA, to release the “Surgeon General’s Framework for Mental Health and Well-Being,” which offers useful broad structure. Based on that framework, here are five key areas to activate: Protection from harm: Take your share of the responsibility for mental health and well-being. That doesn’t mean taking all the share – but being clear that as a leader, you have some work to do in this area. Connection and community: Focus on building a positive, inclusive workplace where people feel a sense of belonging. By putting just a little more attention on relationships, physicians have a tremendous opportunity to shape the culture in your practice or team. Relationships are the number one driver of sustainable mental health (and, research on social determinants of health suggest this is true for physical health as well) – and on retaining and engaging employees. Work-life harmony: Set and respect boundaries, but also recognize autonomy. In the hierarchical nature of health care businesses, physicians sometimes overuse authority which diminishes autonomy. That has a deleterious effect on mental health, and on performance. Mattering at work: Build connection between routine tasks and the meaningful mission. When people can connect the dots between the work they do and the positive impact it has, this meaning at work can mitigate stress. Opportunity for growth: Learning brings a sense of accomplishment. Physicians can do this for themselves by engaging in meaningful learning, and support team members by teaching, mentoring, and offering quality feedback. Healthy Minds, Healthy Workplaces, Healthy People When health care organizations prioritize their own people, they create better results. In a case study using emotional intelligence in preventing burnout, the chief medical officer at Shirley Ryan AbilityLab, Dr. James Sliwa, stresses that the state-of-the-art facilities can only be used at full potential when the doctors and nurses who fill the building are flourishing and motivated. “The physical space is a manifestation of the people who work in it, and how they work together,” says Dr. Sliwa. “And research shows that emotional intelligence is a critical factor in people’s ability to regulate themselves and work effectively with others.” As individuals we are each responsible for our own wellness and we are also an integral part of an organizational system or institution. When we raise awareness and participate in positive practices to support emotional intelligence we can disrupt the cycle of burnout and influence a supportive work environment for all. Note: This article originally appeared in Medical Economics®.

SPECIAL REPORT: TREATMENT-RESISTANT DEPRESSION When initial treatments for depression do not work, patients often feel responsible. They blame themselves, feel stigmatized, and think they are not trying hard enough. Family relationships and work suffer. Life becomes still more constricted and cold. Suicide risk is an ongoing concern. Thus, patients who suffer from treatment-resistant depression (TRD) need and deserve the full range of the best available treatments. An oft-neglected treatment for TRD, both in research studies and in clinical practice, is evidence-based psychotherapy. Indeed, many definitions of TRD focus on medications and somatic treatments and do not even consider psychotherapies. There is a solid research base for the effectiveness of varied psychologically based antidepressant treatments in general. A meta-analysis of 101 studies and more than 11,000 patients found that several psychotherapies are as effective as medication for adult depression, and that combining psychotherapy and pharmacotherapy provides greater effects than either treatment alone. Some evidence indicates that psychotherapy may yield greater durability of treatment gains than pharmacotherapy and that sequential treatment with medication followed by psychotherapy extends durability. In a meta-analysis of 21 studies specifically targeting TRD, psychotherapy added to treatment as usual (TAU) was more effective than TAU alone.9 Another meta-analysis of 18 studies of psychotherapy for treatment nonresponders for any mood or anxiety disorder showed that psychotherapy decreased symptoms and improved quality of life. Among the psychotherapies investigated for TRD, multiple randomized controlled trials have demonstrated the effectiveness of cognitive behavior therapy (CBT) and mindfulness-based cognitive therapy. Other therapies that have fared well in general antidepressant studies but have not had extensive testing for TRD effectiveness include interpersonal psychotherapy (IPT) and brief psychodynamic psychotherapy. Although more research is needed, available evidence suggests that psychotherapy is well worth considering as part of a comprehensive approach to TRD. Key Principles for TRD Several identified mediators of TRD are problems psychotherapy typically addresses. Building hope, resolving interpersonal difficulties, normalizing negative affects instead of regarding them as bad feelings, generating positive attributions, teaching problem-solving, and behavioral activation are the bread and butter of CBT and IPT treatment. Many such targets may not fully respond to somatic interventions. In addition, individuals with chronic depression may have had the illness since childhood or early adult life, and therefore not have developed necessary psychological and social skills that psychotherapy can help them learn. When residual symptoms such as depressed mood or anxiety persist despite medication, evidence-based psychotherapy may reduce these and increase the likelihood of recovery. The therapeutic alliance deserves particular attention in work with patients who have long-standing illness. Acknowledgement of the demoralization and hopelessness that often accompany TRD may improve the relationship with the patient. The scientific literature is rife with implications that treatment resistance means “the patient failing the treatment” when, in fact, it is the other way around. Many patients (and, on occasion, their families) have the sense that there is no hope for a good life. Because such beliefs can counteract recovery, the therapist needs to convey a message of respect for the patient’s efforts and an attitude that one can live a meaningful and productive life, even with residual depressive symptoms. CBT for TRD CBT for TRD focuses on labeling hopelessness a belief and highlighting every new accomplishment as due to efforts by the patient to gradually improve a sense of self-efficacy. Another important aspect of CBT for TRD is helping patients to recognize when they begin to engage in the thinking associated with a negative mood state. Patients may then learn to employ tools that help them disengage from those overlearned mental habits—using thought records, activity scheduling, or mindfulness. Considering these thoughts as a depression mindset that occurs after stressors and can be managed without accelerating a negative mood can be a powerful tool in helping patients with TRD. Planning and managing activity are very important for patients with TRD. Often patients avoid rewarding and meaningful activities because of negative predictions about the outcome. Behavioral activation therapy, employed alone or as part of CBT, encourages the patient to experiment with small increments of activity in pursuit of meaningful goals or potential sources of enjoyment to increase positive affect. In addition, it provides a normalizing rationale for lack of motivation and illustrates the consequences of inactivity.12 Patients can learn to recognize and manage ruminative negative thinking and boost positive moods by augmenting behavioral activation with tools taught in psychotherapy to help them anticipate positive experiences and attend to positive emotions. IPT for TRD IPT focuses on patient emotions and their link to environmental circumstances and relationships.14 Acute treatment is time-limited, typically 12 weekly sessions. The IPT therapist helps the patient define depression as a temporary, treatable (if, for TRD, difficult-to-treat) illness that is not the patient’s fault. This maneuver helps to distinguish the disorder from the patient’s sense of self and relieves guilt. As in CBT, the patient has depression rather than being the depression. Exploring patient history, including previous treatments, yields a therapeutic focus for acute IPT treatment: complicated grief following death of a significant other; a role dispute or struggle with a significant other; a role transition or major life upheaval. The goal of acute treatment is to resolve this crisis. IPT sessions focus on recent interpersonal encounters and how the patient felt during them and handled them. Evoked feelings are explored as useful signals about the environment rather than the bad personal qualities patients often perceive them to be. Normalizing negative affects like anger removes an uncomfortable internal pressure and helps the patient gauge how to read and handle situations more effectively. Role play promotes assertiveness and the use of anger as self-defense in confrontations. No homework is assigned: patient autonomy and the pressure of the time limit determine when the patient acts on items learned in treatment. If IPT, with or without pharmacotherapy, yields acute response or remission, continuation IPT is often warranted to further strengthen functioning and forestall relapse. Short-term psychodynamic psychotherapies have been manualized, tested, and shown to benefit patients with major depression.16 So has brief supportive psychotherapy.17 All these treatments deserve further research, although the National Institute of Mental Health has unfortunately lost interest in funding clinical trials. Concluding Thoughts Patients with TRD live with an ongoing, debilitating disorder for this all-too-frequent condition. Although effective psychotherapy is not a panacea, it deserves more attention as an important contributor to the relief of TRD than it currently receives as well as an increased focus for research for more effective treatments.