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Recent research highlights the potential role of an atypical antipsychotic to treat anxiety, a prevalent and undertreated symptom in bipolar I disorder (BPD). Notably, investigators said, the drug comes without the typical metabolic side effects, including weight gain, associated with this drug class. A post hoc analysis of pooled data from two trials comparing two different doses of cariprazine (Vraylar) to placebo showed it was consistently effective not only in alleviating bipolar depression but also in improving symptoms of anxiety. "Since this was a post hoc analysis, one has to be careful about not overstating the findings," study investigator Roger McIntyre, MD, professor of psychiatry and pharmacology, University of Toronto, Toronto, Ontario, Canada, and head of the Mood Disorders Psychopharmacology Unit, told Medscape Medical News. "But what we can say is that anxiety has been an under-researched, undertreated symptom dimension in BPD, and these findings about cariprazine are very promising," said McIntyre, chair and executive director of the Brain and Cognition Discovery Foundation, Toronto, Canada. The analysis was published in International Clinical Psychopharmacology and was presented as a poster at the 2023 Neuroscience Education Institute, Colorado Springs, Colorado. Ubiquitous, Common, Hazardous Anxiety in BPD is "ubiquitous, common, and hazardous," McIntyre said. "We talk so much about depression and mania as cardinal presentations, but someone could make a case that in that trifecta, we're missing anxiety." In patients with BPD and anxiety, "the index episode is much more difficult to treat, there's a longer time to remission, lower rates of recovery, and a shorter time to recurrence," noted McIntyre, chair of the board of the Depression and Bipolar Support Alliance. Anxiety also may "represent a portent of other things that can add more to the trouble, like alcohol, illicit drugs, or cannabis use — especially now that cannabis is no longer illegal," McIntyre said. Unfortunately, he said, "there hasn't been an organized, systematic approach to developing a therapy for anxiety in BPD." Rather, patients are prescribed benzodiazepines, gabapentinoids, or selective serotonin reuptake inhibitors, all of which have limitations, he added. Some atypical antipsychotics such as quetiapine have been shown to be helpful with anxiety but "have a lot of baggage and side effects — especially sedation, somnolence, weight gain, and metabolic problems," McIntyre noted. Cariprazine is a dopamine D3-preferring D3/D2 partial agonist, a serotonin 5-HT1A receptor partial agonist, and 5-HT2B receptor antagonist, which has shown anxiolytic-like activity in rodent models. It was approved by the US Food and Drug Administration to treat mania, depression, and mixed episodes of BPD in 2015 and BPD in 2019. McIntyre and his team believed there was an opportunity in the completed randomized controlled trials of cariprazine in BPD to conduct a post hoc analysis of its impact on anxiety. 'Cornerstone Mood Stabilizer' The researchers pooled data from two phase 3, randomized, double-blind, placebo-controlled studies in adults with BPD experiencing a current major depressive episode. The pooled intention-to-treat population consisted of 952 patients with BPD (mean age, ~43 years; 62% female) randomized to receive either 1.5 mg/d, 3 mg/d of cariprazine, or placebo. Patients were divided into two subsets: Lower or higher anxiety (defined as a Hamilton Anxiety Rating Scale [HAM-A] total score of < 18 and ≥ 18, respectively). Patients also completed the Montgomery-Åsberg Rating Scale (MADRS). A third of the patients received a placebo, a third received the 1.5 mg/d dose, and a third received the 3 mg/d dose. Demographic and baseline characteristics were similar between the subsets. Results showed there was a statistically significant change in HAM-A total score for cariprazine 1.5 mg/d (P = .0027). The investigators also found a statistically significant change in MADRS total score change for cariprazine 1.5 mg (P = .0200) in the higher anxiety subset. The rate of remission was significantly greater for cariprazine 1.5 mg/d in the higher and lower anxiety subsets (P = .0172 and P = .0004, respectively). In addition, the change in HAM-A total score change was statistically significant for cariprazine 1.5 mg/d in the higher anxiety subgroup (P = .0105) and the 3 mg/d dose in the lower anxiety subgroup (P = .0441). McIntyre hopes these findings can be replicated in other trials. "Clinically, I find that many patients who take cariprazine don't require as many benzodiazepines or other medications for anxiety, and it's one of the better-tolerated medications without metabolic complications or weight gain, so it's become a cornerstone mood stabilizer," he said. Polypharmacy Avoided Another recent study retrospectively analyzed medical records of close to 40 adult patients with BPD I who were receiving treatment with aripiprazole for bipolar depression and then switched to cariprazine. "We wanted to conduct a study in depressed patients who had gained weight on aripiprazole and then directly switched to cariprazine. It improved their mood and helped mitigate weight gain, thereby avoiding polypharmacy of additional antidepressants and weight loss agents," study investigator Maxwell Zachary Price, a medical student at Hackensack Meridian School of Medicine, Nutley, New Jersey, told Medscape Medical News. "In our general outpatient psychiatry practice, we've treated many adult patients with oral aripiprazole for maintenance of BPD," the study's senior investigator, Richard Price, MD, clinical assistant professor of psychiatry at Weill Cornell Medical College, New York City, added. Aripiprazole is associated with weight gain. Moreover, aripiprazole "hasn't shown efficacy in managing BPD," he said. Most patients in Price's practice are insured through Medicaid, which mandates treatment with aripiprazole before covering cariprazine. "We noticed their weight had been creeping up over the years, and they also were experiencing depressive symptoms," he said. The requirement to initiate treatment with aripiprazole before switching to cariprazine offered Price an opportunity to compare the two agents in this real-world setting by retrospectively reviewing the charts of 37 patients with BPD (23 females and 14 males who made the switch). The patients had been taking aripiprazole for a mean duration of 94.9 weeks and had experienced a mean increase in body weight of 16.1% ± 12.3% on aripiprazole before switching. Patients who were taking 2 mg-10 mg of aripiprazole were switched to 1.5 mg of cariprazine, while those taking ≥ 15 mg of aripiprazole were switched to 3 mg of cariprazine. "Patients tolerated the switch well and maintained stability during the transition," and "no patients discontinued cariprazine during the study," Price said. After a mean duration of 36.7 weeks (range, 1-127 weeks), the patients showed a decrease in Clinical Global Impression-Bipolar Severity of Illness Scale score from a mean of 5.0 ± 0.9 to a mean of 2.8 ± 0.7 (t = −12.75, P < .00001). The patients' weight dropped from a mean of 90.3± 21.5 kg on aripiprazole to a mean of 83.9 ± 19.2 kg on cariprazine (t = −4.22, P < .001). Two patients experienced initial nausea that resolved by taking the medication with food, and two experienced initial restlessness that resolved with dosage reduction. "We found that the patients were lighter in mood, body habitus and weight, and less agitated and their mental alertness and concentration improved as well," said Price. He hopes that further research in randomized blinded trials will corroborate the findings. Hypothesis-Generating Research Joseph Cerimele, MD, MPH, associate professor of psychiatry and behavioral sciences, University of Washington, Division of Population Health, UW Medicine, Seattle, Washington, said the research findings are "hypothesis-generating." Ciremele, who wasn't involved with either study, said many clinicians and researchers are trying to tailor treatment options to match patient characteristics, and these studies and other similar research, "help us all ask questions related to concurrent symptoms in bipolar depression." However, the post hoc analysis was a secondary analysis of an efficacy trial where individuals with concurrent anxiety disorders were excluded. "So, a next step might be to evaluate this and other treatments in individuals with BPD and concurrent anxiety disorders," he said. The study by Jain et al was funded by AbbVie. McIntyre had received research grant support from CIHR/GACD/National Natural Science Foundation of China and the Milken Institute; speaker/consultation fees from Lundbeck, Janssen, Alkermes, Neumora Therapeutics Inc., Boehringer Ingelheim, Sage, Biogen, Mitsubishi Tanabe, Purdue, Pfizer, Otsuka, Takeda, Neurocrine, Sunovion, Bausch Health, Axsome Therapeutics, Novo Nordisk, Kris, Sanofi, Eisai, Intra-Cellular Therapies, NewBridge Pharmaceuticals, Viatris, Abbvie, and Atai Life Sciences. McIntyre is the CEO of Braxia Scientific Corp. His coauthors' disclosures are listed in the original paper. Richard Price had received honoraria from AbbVie, Alkermes, Allergan, Intra-Cellular Therapies, Janssen, Jazz, Lundbeck, Neuronetics, Otsuka, and Supernus. Maxwell Price and Cerimele reported no relevant financial relationships. Note: This article originally appeared on Medscape

Conscientiousness, extraversion, and a positive outlook were associated with a lower risk of developing dementia. Psychosocial factors, including personality traits and subjective well-being, were strong predictors of dementia diagnosis but were not predictors of neuropathology at autopsy, according to the findings of a meta-analysis published in the journal Alzheimer’s & Dementia. The big 5 personality traits (conscientiousness, extraversion, openness to experience, neuroticism, and agreeableness) and subjective well-being measures have been associated with dementia, but there is limited concise evidence regarding these risk factors and dementia pathology. To assess the relationship between psychosocial factors and brain pathology, researchers from Northwestern University in the United States searched publication databases for studies that included data about the big 5 and subjective well-being as well as pathology outcomes. A total of 8 longitudinal samples comprising 44,531 (aged 49-81 at baseline; 26%-61% women) patients who were followed up to 21 years were included in this analysis. An increased likelihood of a dementia diagnosis was related with neuroticism (b, 0.11; 95% CI, 0.07-0.15) and negative affect (b, 0.13; 95% CI, 0.003-0.24) whereas dementia was less likely among individuals with conscientiousness (b, -0.15; 95% CI, -0.19 to -0.11), positive affect (b, -0.07; 95% CI, -0.14 to -0.01), extraversion (b, -0.05; 95% CI, -0.09 to -0.009), and openness to experience (b, -0.05; 95% CI, -0.11 to 0.000). Dementia was not related with agreeableness (b, -0.04; 95% CI, -0.09 to 0.01) or satisfaction with life (b, -0.08; 95% CI, -0.16 to 0.006). Across studies, however, there was no consistent association between psychological characteristics and measures of neuropathology. Overall, 3.7% of estimates reached significance using data from individual samples but no significant signals were replicated across samples. In a moderation analysis, 3.2% of assessments reached significance. Of these significant signals, 7.38% of moderators were significant for clinical dementia and 0.92% were significant for neuropathology. For example, a significant interaction between conscientiousness and age was observed on the likelihood of dementia (b, 0.005; 95% CI, 0.002-0.008). The researchers tested whether conscientiousness interacted with a dementia diagnosis to affect the likelihood of neuropathology. They identified no significant association overall (b, 0.10; 95% CI, -0.08 to 0.28) but found that individuals with higher conscientiousness had different Braak stage overall than their clinical dementia diagnosis would indicate. The major limitation of this study was the lack of access to data about neuropathology markers, in which half of samples did not have complete autopsies. “[O]ur results suggest a protective effect of openness to experience, positive affect, and satisfaction with life for incident dementia diagnosis, though effects were less consistent across datasets. Although the Big Five and aspects of [subjective well-being] were not associated with neuropathology at autopsy, moderator analyses reveal some evidence that these psychological factors may also act as predispositions that influence neuropathology.” Note: This article originally appeared on Neurology Advisor

For adults with ADHD, DBT as a treatment strategy demonstrated superior acceptability to clinical management with placebo. A randomized controlled study published in Psychotherapy and Psychosomatics found that dialectical behavior therapy (DBT) demonstrated acceptability as a treatment strategy for adults with attention-deficit/hyperactivity disorder (ADHD), even in the long term. However, future interventions should target treatment adherence to maximize clinical outcomes. When ADHD persists in adulthood, symptoms can affect educational attainment and social and occupational functioning. Adults with ADHD have reported that cognitive behavioral therapy (CBT) and DBT are useful interventions, but few studies have focused on acceptability and adherence to treatment. The Comparison of Methylphenidate and Psychotherapy in Adult ADHD Study (COMPAS; ISRCTN54096201) was a 4-arm study conducted between 2007 and 2013 that compared DBT-based group therapy plus methylphenidate (GBT+MPH) with DBT-based group therapy plus placebo (GBT+PLB), clinical management plus methylphenidate (CM+MPH), and clinical management plus placebo (CM+PLB). The DBT intervention comprised 12 weekly sessions followed by 10 monthly sessions lasting 120 minutes that covered mindfulness, behavior analysis, emotional regulation, impulse control, stress management, and self-respect modules, among others. The clinical management intervention was delivered in 15- to 20-minute individual sessions following the same schedule as DBT and involved supportive counseling to encourage patients to develop coping skills. For this study, researchers evaluated self-reported efficacy of the treatment and adherence, measured by session attendance. The researchers randomly assigned participants to receive GBT+MPH (n=107), GBT+PLB (n=109), CM+MPH (n=110), and CM+PLB (n=107). These cohorts comprised 47.7%, 45.9%, 50.9%, and 54.2% women; were 34.9, 35.6, 35.6, and 34.9 years of age on average; 62.6%, 51.4%, 53.6%, and 62.6% had combined ADHD; and 50.5%, 53.2%, 50%, and 52.3% had used medication treatments for their ADHD, respectively. At week 52, the researchers found that the overall self-reported effectiveness of treatment was significantly greater for CM+MPH than CM+PLB (P <.001), for GPT+PLB than CM+PLB (P <.001), and for GPT+MPH than CM+PLB (P <.001). The patients who received methylphenidate reported significant effects from medication compared with placebo recipients at weeks 52 and 130 (all P £.019). Notably, recipients of DBT with or without active pharmacotherapy reported significant effects from the therapy intervention compared with CM+PLB at week 52 (both P £.002). Among the DBT recipients, self-reported use of skills was associated with significant improvements in Clinical Global Impression (CGI) scores (P <.001), Conners’ Adult ADHD Rating Scale (CAARS) total scores (P <.05), and CAARS ADHD index scores (P <.05). However, the researchers observed no significant group differences in subjective adherence to or effectiveness of overall skills between the GPT+MPH and GPT+PLB groups (all P ³.061). Additionally, the number of unexcused absences from treatment sessions was higher for GPT+PLB than CM+MPH (P =.013) and CM+PLB (P =.028). Consequently, the researchers found that the number of unexcused absences was negatively correlated with the use of skills overall (r = -0.212) and the use of mindfulness (r = -0.194), emotional regulation (r = -0.174), impulse control (r = -0.181), and relationship/self-esteem (r = -0.173) skills. Study authors concluded, “These findings suggest that improving adherence to therapy skills could enhance treatment response.” These study findings may be limited, as the patients who were lost to follow-up were younger and had more severe illness than those who remained in the study. This article originally appeared on Psychiatric Times

US suicide rates reached an all-time high in 2022. Here’s how effective implementation of 988 can help address the problem. 988 - Q&A According to the US Centers for Disease Control and Prevention (CDC), suicide rates reached an all-time high in 2022.1 Psychiatric Times® sat down with Margie Balfour, MD, PhD, of Connections Health Solutions to discuss the 988 Suicide & Crisis Lifeline, its importance in addressing mental health crises, and how hospitals and health care facilities can get involved. Psychiatric Times: Given the alarming increase in suicide rates, 988 has gained significant attention. Can you elaborate on the importance of the 988 initiative and how it can contribute to addressing the current mental health crisis? Margie Balfour, MD, PhD: 988 is a critical piece of our nation’s suicide prevention efforts. 988’s predecessor is the National Suicide Prevention Lifeline—a network of over 200 call centers across the United States that was linked by a common 1-800 number since 2006—and the research on Lifeline call centers shows that callers have reduced thoughts of suicide and feelings of hopelessness after calling.2 988 expands access to this important intervention by linking it to an easy-to-remember, 3-digit number and creating the ability for the public to access it via text and chat. Compared to a year ago, the number of people contacting the Lifeline via text increased nearly tenfold.3 Furthermore, the implementation of 988 has catalyzed an expansion of crisis services overall with increased funding for mobile crisis teams and crisis stabilization facilities.4 The bottom line is that more people have easier access to these life-saving services, and access will continue to increase as these new services grow. PT: A recent National Alliance on Mental Illness (NAMI) poll1 indicates strong public support for federal funding in mental health care, particularly for 988. How can this widespread support translate into meaningful changes in mental health policy and funding priorities? What specific actions or strategies do you believe can help policymakers address the urgent needs outlined in the poll? MB: The broad public and bipartisan support for crisis care is remarkable and creates an opportunity for a once-in-a-generation expansion of crisis services.4 We are in a similar position as the emergency medical services field was in the 1970 to ‘80s following the first 911 call in 1968, and now we cannot imagine life without ambulances, emergency rooms (ERs), etc. States across the nation are building the comparable services for behavioral health emergencies—mobile crisis teams, crisis stabilization facilities, etc. However, thus far most of this work is being financed by Substance Abuse and Mental Health Services Administration (SAMHSA) funds, Medicaid, and other state and local funds, and there are significant disparities in insurance coverage for behavioral health versus medical emergencies.5 More than 220 million Americans with Medicare or private insurance do not have coverage for mobile crisis or crisis stabilization facilities. Ambulances cannot get paid for taking people to a crisis center instead of emergency rooms. These services need parity coverage. We also need to develop clear definitions and standards to describe different types of crisis stabilization facilities,6 similar to how emergency medical systems have trauma center classification (Level 1, Level 2, etc) so that communities can plan crisis systems that can take care of everyone in need. PT: How do you foresee advancements in mental health research contributing to suicide prevention and improved services? Are there specific areas of research or innovation that you find particularly promising in addressing the complex challenges associated with mental health and suicide prevention? MB: I think peer support from people who have lived experience with suicidal thoughts and other behavioral health challenges can be enormously helpful, and there is increasing interest in research to help us better understand how it is helpful, in what situations, for which populations, etc. We also need research to better understand, from a systems perspective, how different crisis services affect outcomes and cost so we can be sure we are building and funding the systems communities need. PT: How are hospitals and health care facilities preparing for the implementation of 988? What challenges and opportunities do you foresee in this transition, and how can health care organizations collaborate to ensure a seamless and effective response to mental health crises? MB: Hospitals can start right now by incorporating 988 and local crisis resources into their discharge planning. Instead of sending patients out of the ER with instructions to call 911 if they have a future crisis, tell them to call 988. If they do have to call 911, educate them on how to ask for an officer with mental health training. Learn about local community resources. Is there a mobile crisis team? Is there a crisis stabilization center they can go to besides the ER? They can also get involved in planning the future crisis system. Every state received planning grants as part of the 988 implementation, and pretty much every community has some kind of group working on this. This is a great opportunity for hospitals to look at what happens to patients with behavioral health emergencies in their system. What happens in the outpatient primary care clinic if someone is suicidal? Instead of calling 911/police, can you work out an arrangement to call 988 or have a mobile crisis team come instead? Some hospitals are building crisis stabilization units attached to their ER or supporting community initiatives to build a freestanding facility. Note: This article originally appeared on Psychiatric Times

Symptoms of anxiety and depression increased in adults living in trigger states that immediately banned abortions after the US Supreme Court Dobbs decision overturned Roe v. Wade, which revoked a woman’s constitutional right to an abortion, new research shows. This could be due to a variety of factors, investigators led by Benjamin Thornburg, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, noted. These include fear about the imminent risk of being denied an abortion, uncertainty around future limitations on abortion and other related rights such as contraception, worry over the ability to receive lifesaving medical care during pregnancy, and a general sense of violation and powerlessness related to loss of the right to reproductive autonomy. The study was published online on January 23, 2024, in JAMA. Mental Health Harm In June 2022, the US Supreme Court overturned Roe vs Wade, removing federal protections for abortion rights. Thirteen states had "trigger laws" that immediately banned or severely restricted abortion — raising concerns this could negatively affect mental health. The researchers used data from the Household Pulse Survey to estimate changes in anxiety and depression symptoms after vs before the Dobbs decision in nearly 160,000 adults living in 13 states with trigger laws compared with roughly 559,000 adults living in 37 states without trigger laws. The mean age of respondents was 48 years, and 51% were women. Anxiety and depression symptoms were measured via the Patient Health Questionnaire-4 (PHQ-4). In trigger states, the mean PHQ-4 score at baseline (before Dobbs) was 3.51 (out of 12) and increased to 3.81 after the Dobbs decision. In nontrigger states, the mean PHQ-4 score at baseline was 3.31 and increased to 3.49 after Dobbs. Living in a trigger state was associated with a small but statistically significant worsening (0.11-point; P < .001) in anxiety/depression symptoms following the Dobbs decision vs living in a nontrigger state, the investigators report. Women aged 18-45 years faced greater worsening of anxiety and depression symptoms following Dobbs in trigger vs nontrigger states, whereas men of a similar age experienced minimal or negligible changes. Implications for Care In an accompanying editorial, Julie Steinberg, PhD, with University of Maryland in College Park, notes the study results provide "emerging evidence that at an individual level taking away reproductive autonomy (by not having legal access to an abortion) may increase symptoms of anxiety and depression in all people and particularly females of reproductive age." These results add to findings from two other studies that examined abortion restrictions and mental health outcomes. Both found that limiting access to abortion was associated with more mental health symptoms among females of reproductive age than among others," Steinberg pointed out. "Together these findings highlight the need for clinicians who practice in states where abortion is banned to be aware that female patients of reproductive age may be experiencing significantly more distress than before the Dobbs decision," Steinberg added. The study received no specific funding. The authors had no relevant conflicts of interest. Steinberg reported serving as a paid expert scientist on abortion and mental health in seven cases challenging abortion policies. Note: This article originally appeared on Medscape

NIH researchers found widespread differences in the brains of children with anxiety disorders that improved after treatment. Researchers at the National Institutes of Health have found overactivation in many brain regions, including the frontal and parietal lobes and the amygdala, in unmedicated children with anxiety disorders. They also showed that treatment with cognitive behavioral therapy (CBT) led to improvements in clinical symptoms and brain functioning. The findings illuminate the brain mechanisms underlying the acute effects of CBT to treat one of the most common mental disorders. The study, published in the American Journal of Psychiatry, was led by researchers at NIH’s National Institute of Mental Health (NIMH). “We know that CBT is effective. These findings help us understand how CBT works, a critical first step in improving clinical outcomes,” said senior author Melissa Brotman, Ph.D., Chief of the Neuroscience and Novel Therapeutics Unit in the NIMH Intramural Research Program. Sixty-nine unmedicated children diagnosed with an anxiety disorder underwent 12 weeks of CBT following an established protocol. CBT, which involves changing dysfunctional thoughts and behaviors through gradual exposure to anxiety-provoking stimuli, is the current gold standard for treating anxiety disorders in children. The researchers used clinician-rated measures to examine the change in children’s anxiety symptoms and clinical functioning from pre- to post-treatment. They also used task-based fMRI to look at whole-brain changes before and after treatment and compare those to brain activity in 62 similarly aged children without anxiety. Children with anxiety showed greater activity in many brain regions, including cortical areas in the frontal and parietal lobes, which are important for cognitive and regulatory functions, such as attention and emotion regulation. The researchers also observed elevated activity in deeper limbic areas like the amygdala, which are essential for generating strong emotions, such as anxiety and fear. Following three months of CBT treatment, children with anxiety showed a clinically significant decrease in anxiety symptoms and improved functioning. Increased activation seen before treatment in many frontal and parietal brain regions also improved after CBT, declining to levels equal to or lower than those of non-anxious children. According to the researchers, the reduced activation in these brain areas may reflect more efficient engagement of cognitive control networks following CBT. However, eight brain regions, including the right amygdala, continued to show higher activity in anxious compared to non-anxious children after treatment. This persistent pattern of enhanced activation suggests some brain regions, particularly limbic areas that modulate responses to anxiety-provoking stimuli, may be less responsive to the acute effects of CBT. Changing activity in these regions may require a longer duration of CBT, additional forms of treatment, or directly targeting subcortical brain areas. “Understanding the brain circuitry underpinning feelings of severe anxiety and determining which circuits normalize and which do not as anxiety symptoms improve with CBT is critical for advancing treatment and making it more effective for all children,” said first author Simone Haller, Ph.D., Director of Research and Analytics in the NIMH Neuroscience and Novel Therapeutics Unit. In this study, all children with anxiety received CBT. For comparison purposes, the researchers also measured brain activity in a separate sample of 87 youth who were at high risk for anxiety based on their infant temperament (for example, showing a high sensitivity to new situations). Because these children were not diagnosed with an anxiety disorder, they had not received CBT treatment. Their brain scans were taken at 10 and 13 years. In adolescents at temperamental risk for anxiety, higher brain activity was related to increased anxiety symptoms over time and matched the brain activity seen in children diagnosed with an anxiety disorder before treatment. This provides preliminary evidence that the brain changes in children with anxiety were driven by CBT and that they may offer a reliable neural marker of anxiety treatment. Anxiety disorders are common in children and can cause them significant distress in social and academic situations. They are also chronic, with a strong link into adulthood when they become harder to treat. Despite the effectiveness of CBT, many children continue to show anxiety symptoms after treatment. Enhancing the therapy to treat anxiety more effectively during childhood can have short- and long-term benefits and prevent more serious problems later in life. This study provides evidence—in a large group of unmedicated youth with anxiety disorders—of altered brain circuitry underlying treatment effects of CBT. The findings could, in time, be used to enhance treatment outcomes by targeting brain circuits linked to clinical improvement. This is particularly important for the subset of children who did not significantly improve after short-term CBT. “The next step for this research is to understand which children are most likely to respond. Are there factors we can assess before treatment begins to make the most informed decisions about who should get which treatment and when? Answering these questions would further translate our research findings into clinical practice,” said Brotman. This article originally appeared on www.nimh.nih.gov

Sleep regularity may be a risk factor for dementia among older individuals. Inconsistent sleep patterns and sleep irregularity may be a risk factor for incident dementia among older individuals, according to study findings published in Neurology. Researchers conducted a study in participants sourced from the UK Biobank, and reported on the link between sleep regularity and risk for incident dementia. The participants were recruited between 2006 and 2010. The Sleep Regularity Index (SRI) was determined by averaging the likelihood of being in the same asleep/wake state at 2 time points which took place 24 hours apart, observed throughout a 7-day accelerometry period. The final analysis comprised a total of 88,094 participants (average age, 65; 56% women) with a median follow-up period of 7.2 years. During this time, there were 480 cases of incident dementia. This group of participants demonstrated a median SRI of 60. Available evidence suggested a non-linear relationship between SRI and the risk for dementia, displaying hazard ratios with a U-shaped pattern. Dementia rates reached their highest point at lower SRI levels, decreased to a minimum around the median (SRI = 60), and then slightly increased with higher SRI levels. When compared to the median SRI of 60, participants with an SRI at the 5th percentile (SRI = 41) had hazard ratios (HRs) of 1.53 (95% CI, 1.24–1.89). Conversely, for individuals with an SRI at the 95th percentile (SRI = 71), the HR was 1.16 (95% CI, 0.89–1.50). The association between SRI and dementia remained consistent throughout the follow-up period. In a subgroup analysis consisting of 15,263 individuals who underwent brain magnetic resonance imaging (MRI), the researchers observed an inverted U-shaped association between SRI and volumes of gray matter (P =.038) and the hippocampus (P =.035). Volumes continued to increase until the SRI reached the median, after which they started to decrease. The researchers also saw a similar association with reduced gray matter volume and hippocampal volume in individuals at the extremes of SRI. They believe that “both extremes if the SRI are linked to adverse brain health outcomes.” The conclusions drawn from this study may have limitations due to the association between SRI and dementia, potential influence from unmeasured confounding factors, and the possibility of reverse causation. “Future studies are required because, even in individuals with normal sleep durations, improvement of sleep timing schedules may represent a potential target for the primary prevention of dementia,” the researchers concluded. This article originally appeared on Neurology Advisor

SPECIAL REPORT: TREATMENT-RESISTANT DEPRESSION DIAGNOSIS The goal of this Special Report is to help you manage treatment-resistant depression (TRD) as best as possible while minimizing harm. This requires first recognizing the kind of depression with which your patient presents to ensure the treatment strategy is the most appropriate. As none of the historical terms (eg, neurotic, psychotic, melancholic) or DSM terms (eg, dysthymia, major depression, mixed features) are distinct biological entities, let us turn to etiology for a better understanding and a refined diagnosis. In my experience, there are 5 kinds of common clinical depression, worth differentiating in that they call for varying treatments (Table). This list is not exhaustive, but the 5 types probably account for most of the depressions seen in clinical practice. Importantly, each type responds best with different approaches. Psychosocial Stressors Halting or decreasing stress is obviously the most direct treatment, but often that is not feasible. Psychosocial stressors can be directly addressed with several forms of psychotherapy. For millennia, the principles of cognitive behavior therapy (CBT) have helped individuals manage situations they cannot change. Aaron T. Beck, MD, a founder of CBT, quoted the Roman emperor Marcus Aurelius: “If thou are pained by any external thing, it is not the thing that disturbs thee, but thine own judgment about it. And it is in thy power to wipe out this judgment now.” Likewise, interpersonal therapy (IPT) could also directly address the source of the problem. But IPT is much less widely available than CBT, especially because a basic version of CBT can be procured via apps that have shown to be nearly as effective as individual CBT from a live therapist, and equally effective if provided with some telephone and text support. Do antidepressants help in chronic psychosocial stress? For many individuals, the answer is yes. However, concern has been raised that the main benefit of antidepressants in this context is an emotional blunting.This sounds like the effects of CBT, but CBT does not blunt other emotional responses, as has been described for antidepressants in 20% to 94% of patients,5 and in asymptomatic volunteers. Childhood Trauma Teicher et al7 noted that childhood trauma is associated with “a cascade of molecular and neurobiological transformations that distinguish patients with maltreatment histories from their nonmaltreated counterparts.” They cited results from the international Study to Predict Optimized Treatment for Depression (NCT00693849), which found that antidepressants led to remission in 84% of patients with no abuse history versus only 16% of those with such a history. Childhood trauma is also associated with a worse outcome in psychotherapy trials.9 However, a recent trial compared cognitive processing therapy (CPT) with a posttraumatic stress disorder (PTSD)-focused variation of dialectical behavior therapy (DBT-PTSD).10 Symptomatic remission, including depression symptoms, was achieved in 58% of the DBT-PTSD participants and 41% of the CPT participants. At minimum, these data suggest that psychotherapy is an important treatment modality to consider for patients with a history of childhood trauma. Medical Conditions and Treatments Depression secondary to a medical condition or treatment may be addressed by resolving the medical issue or switching the medical treatment. However, that too may not be easy or completely feasible. There are some new developments in this area. The advent of neuroactive steroids for postpartum depression is an exciting advance; and yet, as always, any new treatment carries unknown risks that only reveal themselves with years of use. In addition to (or instead of) antidepressants, a modality like behavioral activation therapy (BAT) might be worth considering. For example, the Medical University of South Carolina Hollings Cancer Center is studying an app-based version of BAT11 that has shown evidence of efficacy in depression. Bipolar Depression Patients with TRD have high rates of bipolarity. In one specialty clinic, for instance, 80% of patients referred with TRD had enough bipolarity to warrant switching to a mood stabilizer–based regimen. Failure to recognize subtle bipolarity can lead to multiple trials of antidepressants. For example, in one psychiatric consultation program where undetected bipolarity was common, patients received an average of 2.7 antidepressants before referral. Antidepressants can induce manic episodes and mixed states, although this is relatively uncommon. Thus, antidepressant monotherapy is not recommended in mixed states.17-19 Mood stabilizers are the principal option. When patients are taking a mood stabilizer as well as an antidepressant and are still having mixed state symptoms, clinicians can consider tapering the antidepressant. In one case series, this was associated with a reduction in suicidality as well as anxiety. Although awaiting replication, a study (NCT02519543) from Calkin et al (recipient of the 2023 Best Paper award from the American Society of Clinical Psychopharmacology) suggested that metformin may have an antidepressant effect in select patients with treatment- resistant bipolar depression. Among participants whose insulin resistance reverted to normal on metformin, 80% met response criteria on the Montgomery-Asberg Depression Rating Scale versus 40% of those who did not convert. Other Presentations of MDD The usual list of antidepressant alternatives may be considered (eg, a different psychotherapy; lithium or thyroid augmentation; and light therapy, even in nonseasonal depression), along with some exciting new options. New treatments also have potential applicability in the other kinds of depression. For example, the putative mechanism of psilocybin in depression—Default Mode Network modulation—makes it worth considering for patients with trauma histories as well as major depression. Concluding Thoughts The adage, “When your treatment is not working, question your diagnosis” is still an important one when faced with potential TRD. Are there some treatments that might better target the depression? In reframing the type of depression, we can also reframe what constitutes an “antidepressant,” and choose the safest, most effective treatment for each patient. Although they can be tremendously helpful—indeed, lifesaving—antidepressants carry substantial risks, sometimes with only moderate potential for benefit relative to placebo. With all of this in mind, TRD remains a challenge. The authors contributing to this Special Report will share their perspectives and strategies to further support you and your patients.

SPECIAL REPORT: CLINICAL COMPLICATIONS OF COMORBIDITIES FAQ How can hospital staff provide the most effective care to patients with comorbid medical illness and serious mental illness? Following is a discussion about these comorbidities, the 7 personality types, and best practices for hospital staff to follow in treating patients with each personality type. What Makes Comorbidities Important? Psychiatrists see many patients who have comorbid psychiatric disorders such as a substance use disorder and a mood disorder, or epilepsy and psychogenic nonepileptic seizures. The most common comorbidities are medical disorders and personality traits and/or disorders. Psychiatrists in every setting encounter these individuals; however, the comorbidity is most common in the consultation-liaison experience. Here personality traits or disorders can create problems in the treatment of patients with complex medical illness. Why Does This Happen? Serious medical illness is a regressive experience. The individual who is hospitalized with a serious medical illness is placed in a position of depending on others, akin to the experience of being a child. Regression can be seen as using coping skills from an earlier stage in life or using less mature defenses. The regression can be quite adaptive (eg, allowing other individuals to take care of them without feeling that they have lost control). Patients are typically dressed in hospital gowns; they may have to relinquish control of toileting or feeding. Patients may have to relinquish the accoutrements of business life such as cell phones and computers, and in some cases, they must allow a machine to breathe for them. The individual may accommodate in an adaptive or a maladaptive way, influenced by their personality style. For critically ill patients, the severity of the illness can be maximally disruptive to their typical coping mechanisms. What Are the 7 Personality Types and How Do They Differ in the Ability to Cope With Serious Medical Illness? Kahana and Bibring outlined 7 personality types in 1964.1 Geringer and Stern2 modernized these descriptions in a later paper. The 7 types are dependent, obsessional, histrionic, masochistic, paranoid, narcissistic, and schizoid (Figure1,2). These do not match exactly to the DSM-5-TR personality disorders, but they are useful concepts to understand how different types of individuals cope with illness. For each type there are differences in the meaning of being ill, how the individual interacts with medical staff (transferences), and how staff respond to the individual (countertransference). Managing countertransference and providing care unique to each type of individual can reduce the stress on patient and hospital staff. Can You Review Each of These Personality Types? The dependent personality type tends to be needy, demanding, and clingy. They may be unable to reassure themselves and thus repeatedly seek reassurance from the medical staff. Illness is experienced as a threat of abandonment. Initially, hospital staff may feel important and needed, but the constant need for reassurance leads to staff feeling annoyed or overwhelmed. This may result in them avoiding the patient, which increases the individual’s fear of abandonment. Scheduling time-limited visits, providing realistic reassurance, and employing other resources for supporting the patient help mitigate the negative feelings and create a successful hospital stay. The obsessional personality type likes to feel in control and may be meticulous about details. They may focus on what is “right” or “wrong” in the care they receive. The illness stimulates fears of losing control over their body, emotions, or impulses. Initially we may admire their attention to detail, but repeated questioning, especially when the questions have been thoroughly answered, can feel draining for the staff. The patient may research the illness and therapies, resulting in the physician feeling that the patient does not trust them. Respecting the patient’s need for detail, giving them “homework” between visits, and creating a collaboration with the patient will work against a battle of wills between the patient and the staff. Histrionic patients may initially be entertaining, although they can be melodramatic. They can be enticing and seductive in their interactions with staff. Illness stimulates their fears of not being loved or loss of attractiveness. Initially the patient may seem attractive, but when the patient is seductive, that generates discomfort in the staff who may then confront the patient. Seduction may come in the form of gifts or offering tickets to special events. Maintaining clear boundaries of what is and what is not permissible, providing warmth within a framework of formality, and encouraging the patient to discuss their fears creates an environment in which patient and staff all feel safe. The masochistic patient seems to be a long-suffering, perpetual victim. They may experience illness as a punishment, although this is often not conscious. Such patients may anger staff who think the individual “wants to be ill” or does not want to recover. Staff may feel helpless in their experience of the patient’s apparent need to suffer. Avoid being too positive, which may increase the individual’s unconscious need to suffer. The acceptance of the individual’s experience of suffering, while encouraging them to recover as a “responsibility” to family and friends, can guide the patient through the hospital stay. Paranoid personality types view the world with suspicion. They fear they will be taken advantage of by hospital staff. Illness can be experienced as the world is against them. Medical procedures may be viewed as an exploitation. When kept waiting for a procedure longer than expected, the patient may then refuse the procedure, not accepting that the delay was not targeted at them. Not surprisingly, staff may feel they are being attacked, feel defensive, and experience anger toward the patient. Acknowledging how the patient feels, while presenting the reality of what happens in hospitals, avoids unproductive confrontation. Narcissistic personality types can seem arrogant, self-important, and devaluing of staff. They may question why a student or resident is involved in their care, as they expect the head of the department to be their physician. Illness threatens their fears of being vulnerable and unimportant. They may not have lofty positions in everyday life, but they portray themselves as VIPs with expectations of special treatment. Patients can delay examinations or procedures, claiming they must attend to more important business such as talking on their cellphone. Staff may be treated as though they are inferior to the person, or as being privileged to take care of such an important individual. When devalued by the patient, staff may wish to counterattack with “Who do you think you are?” types of comments. However, these comments only escalate the situation. Encouraging the patient to be collaborative by reframing their entitlement as someone who can understand that not everyone is as perfect as are they helps them to be magnanimous and accepting. Schizoid personalities may appear aloof, remote, or odd. Illness is experienced as a potential and frightening intrusion. Staff may find it difficult to engage with the individual and thus avoid interactions. Maintaining an active involvement, while respecting the individual’s need for privacy, aids in the patient’s treatment; however, not allowing the patient to completely withdraw also is important to a successful hospitalization. These patients benefit from knowing the routine of procedures, meals, and medication administration. Thinking through how each personality type copes with the stress of a serious medical illness prepares us to be the most understanding of their experience. Patients with personality disorders are particularly vulnerable when medically hospitalized. Nevertheless, every patient deserves the best care, which we can help our colleagues provide as part of the consultation-liaison psychiatry interaction both with patients directly and with hospital staff. Post written by Psychiatric Times

This is my prior painting with aspects or elements of St. Louis. Thus, far I have really enjoyed living in St. Louis, based the environment, the culture, the people, the rich history, and amazing architecture. Its been an incredible experience learning how to paint as an adult, as art was a big part of my childhood. I use to love creating art as a child, particularly drawing cars, maybe it has been a long standing obsession =) However, as I got older a majority of my time was dedicated towards academic pursuits that I kind left that enjoyment behind. But, I have learned a lot about life through painting. Painting has taught me that its important to recognize that something that you view as a "mistake" could be easily be corrected and its important not to dwell on such "imperfections". Also doing something consistently will help you become better at a skill or trait, before you leap to negative conclusions about your ability. I think its has taught me to be more creative and free-spirited, as there is no right or wrong way of expressing yourself. Its pretty cool to try new things and challenge yourself to become better at a craft, while enjoying the process and growth. I guess there will never be a destination for me when it comes to art, but rather a journey. Here is another painting I made for my Child Psychiatry program Washington University at St. Louis. If you like my paintings and want to see all of my art collection. You can look at my public social media pages. Follow my Art Page, if interested Source: Vilash Reddy, MD

Gaslighting is a type of manipulation that causes a person to doubt their own beliefs, sanity, or memory. Gaslighters undermine the trust a person has in their reality. They create a world in which the victim’s point of view is untrustworthy, dysfunctional, or wrong. Rather than a single event, gaslighting tends to occur over weeks or years. The gaslighter steadily chips away at the victim’s self-confidence and well-being. Over time, the victim’s self-doubt can lead them to feel confused, scared, and unhappy. Gaslighting can occur in romantic relationships, friendships, families, and in the workplace. Why Do People Gaslight? Gaslighting is often used as a method of control over another person. When someone begins to doubt their own memory or sanity, they may come to depend on the gaslighter to make sense of things. In this way, the gaslighter is elevated to a position of power or authority. Additionally, gaslighting invalidates the victim’s point of view. The victim is made out to be wrong or not to be trusted, so that the gaslighter always has the upper hand in the relationship. The gaslighter becomes the only one in the relationship who can be trusted. How Does Gaslighting Work? The gaslighter convinces the victim they are wrong, misremembering, or are mentally unwell. They might say things such as “that never happened” or “you’re crazy.” Initially, the victim may not be convinced. However, the gaslighter is persistent, and over time the victim comes to believe the gaslighter’s point of view. Gaslighters often enlist others—friends, children, or other family members—to bolster support for their tactics. For example, they may tell others that the victim is “crazy” and is not to be trusted. The Experience of a Gaslighting Victim A victim of gaslighting is likely to feel deep self-doubt. Additionally, they may feel confused, hurt, and sad. How to Defend Against Gaslighting

Imposter Syndrome: Why You May Feel Like a Fraud Imposter syndrome is that uncomfortable feeling you experience when you think you're unqualified and incompetent. You might look around and assume everyone knows what they're doing except you. And if you achieve something good, you'll chalk your accomplishments up to “good luck.” It’s normal to feel out of place or doubt yourself occasionally. But if you have these feelings most of the time, you may be experiencing imposter syndrome. Imposter syndrome refers to long-lasting feelings of unworthiness that don’t match up with the facts or others’ perceptions. The key feature of imposter syndrome is a persistent fear of being exposed as a fraud.