Integrative transcriptome- and DNA methylation analysis of brain tissue from the temporal pole in suicide decedents and their controls.

Suicide rates have increased steadily world-wide over the past two decades, constituting a serious public health crisis that creates a significant burden to affected families and the society as a whole. Suicidal behavior involves a multi-factorial etiology, including psychological, social and biological factors. Since the molecular neural mechanisms of suicide remain vastly uncharacterized, we examined transcriptional- and methylation profiles of postmortem brain tissue from subjects who died from suicide as well as their neurotypical healthy controls. We analyzed temporal pole tissue from 61 subjects, largely free from antidepressant and antipsychotic medication, using RNA-sequencing and DNA-methylation profiling using an array that targets over 850,000 CpG sites. Expression of NPAS4, a key regulator of inflammation and neuroprotection, was significantly downregulated in the suicide decedent group. Moreover, we identified a total of 40 differentially methylated regions in the suicide decedent group, mapping to seven genes with inflammatory function. There was a significant association between NPAS4 DNA methylation and NPAS4 expression in the control group that was absent in the suicide decedent group, confirming its dysregulation. NPAS4 expression was significantly associated with the expression of multiple inflammatory factors in the brain tissue. Overall, gene sets and pathways closely linked to inflammation were significantly upregulated, while specific pathways linked to neuronal development were suppressed in the suicide decedent group. Excitotoxicity as well as suppressed oligodendrocyte function were also implicated in the suicide decedents. In summary, we have identified central nervous system inflammatory mechanisms that may be active during suicidal behavior, along with oligodendrocyte dysfunction and altered glutamate neurotransmission. In these processes, NPAS4 might be a master regulator, warranting further studies to validate its role as a potential biomarker or therapeutic target in suicidality.

Implications of Online Self-Diagnosis in Psychiatry.

Online self-diagnosis of psychiatric disorders by the general public is increasing. The reasons for the increase include the expansion of Internet technologies and the use of social media, the rapid growth of direct-to-consumer e-commerce in healthcare, and the increased emphasis on patient involvement in decision making. The publicity given to artificial intelligence (AI) has also contributed to the increased use of online screening tools by the general public. This paper aims to review factors contributing to the expansion of online self-diagnosis by the general public, and discuss both the risks and benefits of online self-diagnosis of psychiatric disorders. A narrative review was performed with examples obtained from the scientific literature and commercial articles written for the general public. Online self-diagnosis of psychiatric disorders is growing rapidly. Some people with a positive result on a screening tool will seek professional help. However, there are many potential risks for patients who self-diagnose, including an incorrect or dangerous diagnosis, increased patient anxiety about the diagnosis, obtaining unfiltered advice on social media, using the self-diagnosis to self-treat, including online purchase of medications without a prescription, and technical issues including the loss of privacy. Physicians need to be aware of the increase in self-diagnosis by the general public and the potential risks, both medical and technical. Psychiatrists must recognize that the general public is often unaware of the challenging medical and technical issues involved in the diagnosis of a mental disorder, and be ready to treat patients who have already obtained an online self-diagnosis.

Perceived Barriers to Using Neurostimulation: A National Survey of Psychiatrists, Patients, Caregivers, and the General Public.

OBJECTIVES: Neurostimulation interventions often face heightened barriers limiting patient access. The objective of this study is to examine different stakeholders' perceived barriers to using different neurostimulation interventions for depression. METHODS: We administered national surveys with an embedded experiment to 4 nationwide samples of psychiatrists (n = 505), people diagnosed with depression (n = 1050), caregivers of people with depression (n = 1026), and members of the general public (n = 1022). We randomly assigned respondents to 1 of 8 conditions using a full factorial experimental design: 4 neurostimulation modalities (electroconvulsive therapy [ECT], repetitive transcranial magnetic stimulation [rTMS], deep brain stimulation [DBS], or adaptive brain implants [ABIs]) by 2 depression severity levels (moderate or severe). We asked participants to rank from a list what they perceived as the top 3 barriers to using their assigned intervention. We analyzed the data with analysis of variance and logistic regression. RESULTS: Nonclinicians most frequently reported "limited evidence of the treatment's effectiveness" and "lack of understanding of intervention" as their top 2 most important practical barriers to using ECT and TMS, respectively. Compared with nonclinicians, psychiatrists were more likely to identify "stigma about treatment" for ECT and "lack of insurance coverage" for TMS as the most important barriers. CONCLUSIONS: Overall, psychiatrists' perceptions of the most important barriers to using neurostimulation interventions were significantly different than those of nonclinicians. Perceived barriers were significantly different for implantable DBS and ABI) versus nonimplantable (rTMS and ECT) neurostimulation interventions. Better understanding of how these barriers vary by neurostimulation and stakeholder group could help us address structural and attitudinal barriers to effective use of these interventions.

Relapse prevention through health technology program reduces hospitalization in schizophrenia.

BACKGROUND: Psychiatric hospitalization is a major driver of cost in the treatment of schizophrenia. Here, we asked whether a technology-enhanced approach to relapse prevention could reduce days spent in a hospital after discharge. METHODS: The Improving Care and Reducing Cost (ICRC) study was a quasi-experimental clinical trial in outpatients with schizophrenia conducted between 26 February 2013 and 17 April 2015 at 10 different sites in the USA in an outpatient setting. Patients were between 18 and 60 years old with a diagnosis of schizophrenia, schizoaffective disorder, or psychotic disorder not otherwise specified. Patients received usual care or a technology-enhanced relapse prevention program during a 6-month period after discharge. The health technology program included in-person, individualized relapse prevention planning with treatments delivered via smartphones and computers, as well as a web-based prescriber decision support program. The main outcome measure was days spent in a psychiatric hospital during 6 months after discharge. RESULTS: The study included 462 patients, of which 438 had complete baseline data and were thus used for propensity matching and analysis. Control participants (N = 89; 37 females) were enrolled first and received usual care for relapse prevention followed by 349 participants (128 females) who received technology-enhanced relapse prevention. During 6-month follow-up, 43% of control and 24% of intervention participants were hospitalized (χ2 = 11.76, p<0.001). Days of hospitalization were reduced by 5 days (mean days: b = -4.58, 95% CI -9.03 to -0.13, p = 0.044) in the intervention condition compared to control. CONCLUSIONS: These results suggest that technology-enhanced relapse prevention is an effective and feasible way to reduce rehospitalization days among patients with schizophrenia.

Blood-based biomarkers of antidepressant response to ketamine and esketamine: A systematic review and meta-analysis.

(R,S)-ketamine (ketamine) and its enantiomer (S)-ketamine (esketamine) can produce rapid and substantial antidepressant effects. However, individual response to ketamine/esketamine is variable, and there are no well-accepted methods to differentiate persons who are more likely to benefit. Numerous potential peripheral biomarkers have been reported, but their current utility is unclear. We conducted a systematic review/meta-analysis examining the association between baseline levels and longitudinal changes in blood-based biomarkers, and response to ketamine/esketamine. Of the 5611 citations identified, 56 manuscripts were included (N = 2801 participants), and 26 were compatible with meta-analytical calculations. Random-effect models were used, and effect sizes were reported as standardized mean differences (SMD). Our assessments revealed that more than 460 individual biomarkers were examined. Frequently studied groups included neurotrophic factors (n = 15), levels of ketamine and ketamine metabolites (n = 13), and inflammatory markers (n = 12). There were no consistent associations between baseline levels of blood-based biomarkers, and response to ketamine. However, in a longitudinal analysis, ketamine responders had statistically significant increases in brain-derived neurotrophic factor (BDNF) when compared to pre-treatment levels (SMD [95% CI] = 0.26 [0.03, 0.48], p = 0.02), whereas non-responders showed no significant changes in BDNF levels (SMD [95% CI] = 0.05 [-0.19, 0.28], p = 0.70). There was no consistent evidence to support any additional longitudinal biomarkers. Findings were inconclusive for esketamine due to the small number of studies (n = 2). Despite a diverse and substantial literature, there is limited evidence that blood-based biomarkers are associated with response to ketamine, and no current evidence of clinical utility.

Telepsychiatry in an Era of Digital Mental Health Startups.

PURPOSE OF REVIEW: Telepsychiatry practiced by psychiatrists is evidence-based, regulated, private, and effective in diverse settings. The use of telemedicine has grown since the COVID-19 pandemic as people routinely obtain more healthcare services online. At the same time, there has been a rapid increase in the number of digital mental health startups that offer various services including online therapy and access to prescription medications. These digital mental health firms advertise directly to the consumer primarily through digital advertising. The purpose of this narrative review is to contrast traditional telepsychiatry and the digital mental health market related to online therapy. RECENT FINDINGS: In contrast to standard telepsychiatry, most of the digital mental health startups are unregulated, have unproven efficacy, and raise concerns related to self-diagnosis, self-medicating, and inappropriate prescribing. The role of digital mental health firms for people with serious mental illness has not been determined. There are inadequate privacy controls for the digital mental health firms, including for online therapy. We live in an age where there is widespread admiration for technology entrepreneurs and increasing emphasis on the role of the patient as a consumer. Yet, the business practices of digital mental health startups may compromise patient safety for profits. There is a need to address issues with the digital mental health startups and to educate patients about the differences between standard medical care and digital mental health products.

Ulotaront: review of preliminary evidence for the efficacy and safety of a TAAR1 agonist in schizophrenia.

Ulotaront is a trace amine-associated receptor 1 (TAAR1) agonist in Phase 3 clinical development for the treatment of schizophrenia. Ulotaront was discovered through a unique, target-agnostic approach optimized to identify drug candidates lacking D2 and 5-HT2A receptor antagonism, while demonstrating an antipsychotic-like phenotypic profile in vivo. The mechanism of action (MOA) of ulotaront is thought to be mediated by agonism at TAAR1 and serotonin 5-HT1A receptors. Ulotaront has completed two Phase 2 trials (4-week acute study and 26-week open-label extension) which led to Breakthrough Therapy Designation from the US Food and Drug Administration for the treatment of schizophrenia. In the double-blind, placebo-controlled, acute study, ulotaront was associated with significant (p < 0.001) improvement in Positive and Negative Syndrome Scale (PANSS) total score (effect size [ES]: 0.45), with improvements vs. placebo also observed across secondary endpoints. Post-hoc analyses of the acute trial revealed additional evidence to support the effect of ulotaront on negative symptoms. In the 4-week study, ulotaront was well-tolerated, with an incidence of adverse events (AEs) numerically lower compared to placebo (45.8% vs. 50.4%; with a number needed to harm [NNH] for individual ulotaront AEs all > 40). The open-label extension demonstrated further improvement across schizophrenia symptoms and confirmed the tolerability of ulotaront, with a 6-month completion rate of 67%. Based on current data, ulotaront shows potential to be a first-in-class TAAR1 agonist for the treatment of schizophrenia with a safety and efficacy profile distinct from current antipsychotics.

Challenges and Ethical Considerations to Successfully Implement Artificial Intelligence in Clinical Medicine and Neuroscience: a Narrative Review.

This narrative review discusses how the safe and effective use of clinical artificial intelligence (AI) prediction tools requires recognition of the importance of human intelligence. Human intelligence, creativity, situational awareness, and professional knowledge, are required for successful implementation. The implementation of clinical AI prediction tools may change the workflow in medical practice resulting in new challenges and safety implications. Human understanding of how a clinical AI prediction tool performs in routine and exceptional situations is fundamental to successful implementation. Physicians must be involved in all aspects of the selection, implementation, and ongoing product monitoring of clinical AI prediction tools.

Contributions of common genetic variants to risk of schizophrenia among individuals of African and Latino ancestry.

Schizophrenia is a common, chronic and debilitating neuropsychiatric syndrome affecting tens of millions of individuals worldwide. While rare genetic variants play a role in the etiology of schizophrenia, most of the currently explained liability is within common variation, suggesting that variation predating the human diaspora out of Africa harbors a large fraction of the common variant attributable heritability. However, common variant association studies in schizophrenia have concentrated mainly on cohorts of European descent. We describe genome-wide association studies of 6152 cases and 3918 controls of admixed African ancestry, and of 1234 cases and 3090 controls of Latino ancestry, representing the largest such study in these populations to date. Combining results from the samples with African ancestry with summary statistics from the Psychiatric Genomics Consortium (PGC) study of schizophrenia yielded seven newly genome-wide significant loci, and we identified an additional eight loci by incorporating the results from samples with Latino ancestry. Leveraging population differences in patterns of linkage disequilibrium, we achieve improved fine-mapping resolution at 22 previously reported and 4 newly significant loci. Polygenic risk score profiling revealed improved prediction based on trans-ancestry meta-analysis results for admixed African (Nagelkerke's R2 = 0.032; liability R2 = 0.017; P < 10-52), Latino (Nagelkerke's R2 = 0.089; liability R2 = 0.021; P < 10-58), and European individuals (Nagelkerke's R2 = 0.089; liability R2 = 0.037; P < 10-113), further highlighting the advantages of incorporating data from diverse human populations.

They Affect the Person, but for Better or Worse? Perceptions of Electroceutical Interventions for Depression Among Psychiatrists, Patients, and the Public.

Responding to reports of cases of personality change following deep brain stimulation, neuroethicists have debated the nature and ethical implications of these changes. Recently, this literature has been challenged as being overblown and therefore potentially an impediment to patients accessing needed treatment. We interviewed 16 psychiatrists, 16 patients with depression, and 16 members of the public without depression, all from the Midwestern United States, about their views on how three electroceutical interventions (deep brain stimulation, electroconvulsive therapy, and transcranial magnetic stimulation) used to treat depression might affect the self. Participants were also asked to compare the electroceuticals' effects on the self with the effects of commonly used depression treatments (psychotherapy and pharmaceuticals). Using qualitative content analysis, we found that participants' views on electroceuticals' potential effects on the self mainly focused on treatment effectiveness and side effects. Our results have implications for both theoretical discussions in neuroethics and clinical practice in psychiatry.

Beyond the Cuckoo's Nest: Patient and Public Attitudes about Psychiatric Electroceutical Interventions.

Recent research emphasizes the role of psychiatric electroceutical interventions (PEIs), bioelectronic treatments that employ electrical stimulation to affect and modify brain function, to effectively treat psychiatric disorders. We sought to examine attitudes about three PEIs-electroconvulsive therapy, transcranial magnetic stimulation, and deep brain stimulation-among patients with depression and members of the general public. As part of a larger study to assess different stakeholders' attitudes about PEIs, we conducted semi-structured key informant interviews with 16 individuals living with depression and 16 non-depressive members of the general public. We used a purposive sampling approach to recruit potential participants based on eligibility criteria. We performed qualitative content analysis of interview transcripts. Participants from both groups expressed an overall cautionary attitude towards PEIs, yet there were mixed attitudes in both groups. Patients commonly described electroconvulsive therapy as scary, traumatic, or intense, while members of the general public often referenced the treatment's negative portrayal in One Flew over the Cuckoo's Nest. Patients and the general public saw transcranial magnetic stimulation as a potentially viable option, but in most cases only if medication was not effective. Deep brain stimulation attitudes were predominantly negative among patients and cautionary among public. The overall cautionary attitudes towards PEIs, together with the technological features and social aspects underlying those attitudes, highlight the need for unbiased education to fill the gaps in knowledge and inform perceptions of those who may benefit from these treatments.

International Consortium on the Genetics of Electroconvulsive Therapy and Severe Depressive Disorders (Gen-ECT-ic).

Recent genome-wide association studies have demonstrated that the genetic burden associated with depression correlates with depression severity. Therefore, conducting genetic studies of patients at the most severe end of the depressive disorder spectrum, those with treatment-resistant depression and who are prescribed electroconvulsive therapy (ECT), could lead to a better understanding of the genetic underpinnings of depression. Despite ECT being one of the most effective forms of treatment for severe depressive disorders, it is usually placed at the end of treatment algorithms of current guidelines. This is perhaps because ECT has controlled risk and logistical demands including use of general anaesthesia and muscle relaxants and side-effects such as short-term memory impairment. Better understanding of the genetics and biology of ECT response and of cognitive side-effects could lead to more personalized treatment decisions. To enhance the understanding of the genomics of severe depression and ECT response, researchers and ECT providers from around the world and from various depression or ECT networks, but not limited to, such as the Psychiatric Genomics Consortium, the Clinical Alliance and Research in ECT, and the National Network of Depression Centers have formed the Genetics of ECT International Consortium (Gen-ECT-ic). Gen-ECT-ic will organize the largest clinical and genetic collection to date to study the genomics of severe depressive disorders and response to ECT, aiming for 30,000 patients worldwide using a GWAS approach. At this stage it will be the largest genomic study on treatment response in depression. Retrospective data abstraction and prospective data collection will be facilitated by a uniform data collection approach that is flexible and will incorporate data from many clinical practices. Gen-ECT-ic invites all ECT providers and researchers to join its efforts.

Safety and utility of acute electroconvulsive therapy for agitation and aggression in dementia.

OBJECTIVE: Agitation and aggression are among the most frequent and disruptive behavioral complications of dementia that contribute to increased cost of care, hospitalization, caregiver burden, and risk of premature institutionalization. This current study examined the safety and efficacy of electroconvulsive therapy (ECT) as a treatment for behavioral disturbances in dementia. We hypothesized that ECT would result in reduced agitated and aggressive behaviors between baseline and discharge. METHODS: Twenty-three participants admitted to McLean Hospital (Belmont, MA, USA) and Pine Rest Christian Mental Health Services (Grand Rapids, MI, USA), with a diagnosis of dementia who were referred for ECT to treat agitation and/or aggression, were enrolled in the study. We administered the Cohen-Mansfield Agitation Inventory-Short Form, Neuropsychiatric Inventory-Nursing Home Version, Cornell Scale for Depression in Dementia, and the Clinical Global Impression Scale at baseline, during, and after the ECT course. RESULTS: Regression analyses revealed a significant decrease from baseline to discharge on the Cohen-Mansfield Agitation Inventory (F(4,8) = 13.3; p = 0.006) and Neuropsychiatric Inventory (F(4,31) = 14.6; p < 0.001). There was no statistically significant change in scores on the Cornell Scale for Depression in Dementia. The Clinical Global Impression scores on average changed from a rating of "markedly agitated/aggressive" at baseline to "borderline agitated/aggressive" at discharge. Treatment with ECT was well tolerated by most participants; discontinuation of ECT occurred for two participants because of recurrence of agitation and for three participants because of adverse events. CONCLUSIONS: Electroconvulsive therapy may be a safe treatment option to reduce symptoms of agitation and aggression in patients with dementia whose behaviors are refractory to medication management.

Adding urine and saliva toxicology to SBIRT for drug screening of new patients.

BACKGROUND AND OBJECTIVES: To determine illicit drug use among new patients in primary medical care who denied using "street drugs" during Screening, Brief Intervention and Referral to Treatment (SBIRT). METHODS: 96 new patients who denied use of "street drugs" were tested for drugs as part of routine SBIRT screening. RESULTS: Of those tested, 14.6% of those with urine specimens and 4.1% of those with saliva specimens tested positive for illicit drugs. DISCUSSION AND CONCLUSIONS: Drug toxicology can detect unreported illicit drug use during SBIRT screening, with urine being superior to saliva. SCIENTIFIC SIGNIFICANCE: Drug toxicology can increase the effectiveness of SBIRT screening in primary care medical clinics.

Maintenance treatment with varenicline for smoking cessation in patients with schizophrenia and bipolar disorder: a randomized clinical trial.

IMPORTANCE: It is estimated that more than half of those with serious mental illness smoke tobacco regularly. Standard courses of pharmacotherapeutic cessation aids improve short-term abstinence, but most who attain abstinence relapse rapidly after discontinuation of pharmacotherapy. OBJECTIVE: To determine whether smokers diagnosed with schizophrenia and bipolar disease have higher rates of prolonged tobacco abstinence with maintenance pharmacotherapy than with standard treatment. DESIGN, SETTING, AND PARTICIPANTS: Randomized, double-blind, placebo-controlled, parallel-group, relapse-prevention clinical trial conducted in 10 community mental-health centers. Of 247 smokers with schizophrenia or bipolar disease recruited from March 2008-April 2012, 203 received 12-weeks' open-label varenicline and cognitive behavioral therapy and 87 met abstinence criteria to enter the relapse prevention intervention. INTERVENTIONS: Participants who had 2 weeks or more of continuous abstinence at week 12 of open treatment were randomly assigned to receive cognitive behavioral therapy and double-blind varenicline (1 mg, 2 per day) or placebo from weeks 12 to 52. Participants then discontinued study treatment and were followed up to week 76. MAIN OUTCOMES AND MEASURES: Seven-day rate of continuous abstinence at study week 52, the end of the relapse-prevention phase, confirmed by exhaled carbon monoxide. Secondary outcomes were continuous abstinence rates for weeks 12 through 64 based on biochemically verified abstinence and weeks 12 through 76, based on self-reported smoking behavior. RESULTS: Sixty-one participants completed the relapse-prevention phase; 26 discontinued participation (7 varenicline, 19 placebo) and were considered to have relapsed for the analyses; 18 of these had relapsed prior to dropout. At week 52, point-prevalence abstinence rates were 60% in the varenicline group (24 of 40) vs 19% (9 of 47) in the placebo group (odds ratio [OR], 6.2; 95% CI, 2.2-19.2; P < .001). From weeks 12 through 64, 45% (18 of 40) among those in the varenicline group vs 15% (7 of 47) in the placebo group were continuously abstinent (OR, 4.6; 95% CI, 1.5-15.7; P = .004), and from weeks 12 through 76, 30% (12 of 40) in the varenicline group vs 11% (5 of 47) in the placebo group were continuously abstinent (OR, 3.4; 95% CI, 1.02-13.6; P = .03). There were no significant treatment effects on psychiatric symptom ratings or psychiatric adverse events. CONCLUSIONS AND RELEVANCE: Among smokers with serious mental illness who attained initial abstinence with standard treatment, maintenance pharmacotherapy with varenicline and cognitive behavioral therapy improved prolonged tobacco abstinence rates compared with cognitive behavioral therapy alone after 1 year of treatment and at 6 months after treatment discontinuation. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00621777.

The differential effects of psychiatrists' and patients' prior experiences on views about psychiatric electroceutical interventions.

The aim of this study is to examine ways in which prior experiences and familiarity with psychiatric electroceutical interventions (PEI) shape psychiatrists' and patients' views about these interventions. We administered a national survey, with an embedded experiment, to psychiatrists (n = 505) and adults diagnosed with depression (n = 1050). We randomly assigned respondents to one of 8 conditions using a full factorial experimental design: 4 PEI modalities [ECT, rTMS, DBS, or adaptive brain implants (ABIs)] by 2 depression severity levels [moderate or severe]. We analyzed the survey data with ANOVA and OLS linear regression models. Patients having experience with any PEI reported more positive affect toward, but also greater perceived risk from, their assigned PEI than did patients with no such experience. Psychiatrists who referred or administered any PEI reported more positive affect toward and greater perceived influence on self and perceived benefit from their assigned PEI than did psychiatrists with no such familiarity. Limitations of our study include that our participants were randomly assigned to a PEI, not necessarily to the one they had experience with. Moreover, our study did not directly ask about the kind of experiences participants had with a given PEI. Overall, our survey data shows that greater experience with PEIs elicits more positive affect in both stakeholder groups. Beyond this, prior PEI experience shapes attitudes towards these interventions in complex ways. Further research linking different types of experience with a given PEI would help better understand factors shaping attitudes about specific PEIs.

Association between sociodemographic factors, clinic characteristics and mental health screening rates in primary care.

BACKGROUND: Screening for mental health problems has been shown to be effective to detect depression and initiate treatment in primary care. Current guidelines recommend periodic screening for depression and anxiety. This study examines the association of patient sociodemographic factors and clinic characteristics on mental health screening in primary care. DESIGN: In this retrospective cohort study, electronic medical record (EMR) data from a 14-month period from 10/15/2021 to 12/14/2022 were analyzed. Data were retrieved from 18 primary care clinics from the Corewell Health healthcare system in West Michigan. The main outcome was documentation of any Patient Health Questionnaire (PHQ-4/PHQ-9/GAD-7) screening in the EMR within the 14-month period at patient level. General linear regression models with logit link function were used to assess adjusted odds ratio (aOR) of having a documented screening. RESULTS: In total, 126,306 unique patients aged 16 years or older with a total of 291,789 encounters were included. The prevalence of 14-month screening was 79.8% (95% CI, 79.6-80.0). Regression analyses revealed higher screening odds for patients of smaller clinics (<5,000 patients, aOR 1.88; 95% CI 1.80-1.98 vs. clinics >10.000 patients), clinics in areas with mental health provider shortages (aOR 1.69; 95% CI 1.62-1.77), frequent visits (aOR 1.80; 95% CI, 1.78-1.83), and having an annual physical / well child visit encounter (aOR 1.52; 95% CI, 1.47-1.57). Smaller positive effect sizes were also found for male sex, Black or African American race, Asian race, Latinx ethnicity (ref. White/Caucasians), and having insurance through Medicaid (ref. other private insurance). DISCUSSION: The 14-month mental health screening rates have been shown to be significantly lower among patients with infrequent visits seeking care in larger clinics and available mental health resources in the community. Introducing and incentivizing mandatory mental health screening protocols in annual well visits, are viable options to increase screening rates.

Abnormal Oculomotor Corollary Discharge Signaling as a Trans-diagnostic Mechanism of Psychosis.

BACKGROUND AND HYPOTHESIS: Corollary discharge (CD) signals are "copies" of motor signals sent to sensory areas to predict the corresponding input. They are a posited mechanism enabling one to distinguish actions generated by oneself vs external forces. Consequently, altered CD is a hypothesized mechanism for agency disturbances in psychosis. Previous studies have shown a decreased influence of CD signals on visual perception in individuals with schizophrenia-particularly in those with more severe positive symptoms. We therefore hypothesized that altered CD may be a trans-diagnostic mechanism of psychosis. STUDY DESIGN: We examined oculomotor CD (using the blanking task) in 49 participants with schizophrenia or schizoaffective disorder (SZ), 36 bipolar participants with psychosis (BPP), and 40 healthy controls (HC). Participants made a saccade to a visual target. Upon saccade initiation, the target disappeared and reappeared at a horizontally displaced position. Participants indicated the direction of displacement. With intact CD, participants can make accurate perceptual judgements. Otherwise, participants may use saccade landing site as a proxy of pre-saccadic target to inform perception. Thus, multi-level modeling was used to examine the influence of target displacement and saccade landing site on displacement judgements. STUDY RESULTS: SZ and BPP were equally less sensitive to target displacement than HC. Moreover, regardless of diagnosis, SZ and BPP with more severe positive symptoms were more likely to rely on saccade landing site. CONCLUSIONS: These results suggest that altered CD may be a trans-diagnostic mechanism of psychosis.

Change in neurocognitive functioning in patients with treatment-resistant depression with serial intravenous ketamine infusions: The Bio-K multicenter trial.

This nonrandomized, multicenter, open-label clinical trial explored the impact of intravenous (IV) ketamine on cognitive function in adults (n = 74) with treatment-resistant depression (TRD). Patients received three IV ketamine infusions during the acute phase and, if remitted, four additional infusions in the continuation phase (Mayo site). Cognitive assessments using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) were conducted at baseline, end of the acute phase, and end of the continuation phase (Mayo site). Results showed a significant 53 % (39/74) remission rate in depression symptoms after the acute phase. In adjusted models, baseline language domain score was associated with a higher odd of remission (Odds Ratio, 1.09, 95 % CI = 1.03-1.17, p = 0.004) and greater improvement in MADRS at the end of the acute phase (ß =-0.97; 95 % CI, -1.74 to -0.20; P = 0.02). The likelihood of remission was not significantly associated with baseline immediate or delayed memory, visuospatial/constructional, or attention scores. In the continuation phase, improvements in immediate and delayed memory and attention persisted, with additional gains in visuospatial and language domains. Limitations included an open-label design, potential practice effects, and ongoing psychotropic medication use. Overall, the study suggests cognitive improvement, not deterioration, associated with serial IV ketamine administrations for TRD. These findings encourage future studies with larger sample sizes and longer follow-up periods to examine any potential for deleterious effect with recurrent ketamine use for TRD. Trial Registration: ClinicalTrials.gov: NCT03156504.

High-dose oral ziprasidone versus conventional dosing in schizophrenia patients with residual symptoms: the ZEBRAS study.

Uncontrolled studies have suggested that increasing the dose of ziprasidone above the standard maximum daily dose of 160 mg may be more effective for some patients with schizophrenia. To test this hypothesis, we conducted an 8-week, placebo-controlled, fixed-dose escalation trial comparing ziprasidone 160 versus 320 mg/d in individuals with schizophrenia or schizoaffective disorder who remained symptomatic despite treatment with ziprasidone 160 mg/d for at least 3 weeks. Of 75 randomized patients, 42 completed the study. Serum ziprasidone concentrations increased significantly in the high-dose group compared with the standard-dose group at week 4 but did not differ between groups at week 8. Both treatment groups exhibited significant symptomatic improvement. Response did not differ between treatment groups; however, in the high-dose group, higher ziprasidone serum concentrations were associated with better response at a trend level. Higher ziprasidone concentrations were also associated with reductions in diastolic blood pressure and, at a trend level, with more prominent negative symptoms and greater QTc prolongation. In summary, increasing the ziprasidone dose to 320 mg/d did not produce a sustained elevation in serum concentrations or symptomatic improvement compared with a standard ziprasidone dose of 160 mg/d.