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Validated, multicomponent treatments designed to address symptoms and functioning of individuals at clinical high risk for psychosis are currently lacking. The authors report findings of a study with such individuals participating in step-based care-a program designed to provide low-intensity, non-psychosis-specific interventions and advancement to higher-intensity, psychosis-specific interventions only if an individual is not meeting criteria for a clinical response. Among individuals with symptomatic or functional concerns at enrollment, 67% met criteria for a symptomatic response (median time to response=11.1 weeks), and 64% met criteria for a functional response (median time to response=8.9 weeks)., Competing Interests: Dr. Guirgis reports providing consultation to Karuna Therapeutics. The other authors report no financial relationships with commercial interests.

Recent COVID-19-related federal legislation has resulted in time-limited increases in Mental Health Block Grant (MHBG) set-aside dollars for coordinated specialty care (CSC) throughout the United States. The state of Ohio has opted to apply these funds to establish a learning health network of Ohio CSC teams, promote efforts to expand access to CSC, and quantify the operating costs and rates of reimbursement from private and public payers for these CSC teams. These efforts may provide other states with a model through which they can apply increased MHBG funds to support the success of their own CSC programs., Competing Interests: Dr. Breitborde reports serving as an external consultant to Arizona Complete Health. The other authors report no financial relationships with commercial interests.

Background: Clozapine, an antipsychotic medication used to treat treatment-refractory schizophrenia, has been associated with various dangerous side effects, including myocarditis. However, there have been few published cases reporting on patients with clozapine-induced myocarditis confirmed by cardiac magnetic resonance imaging or the management, treatment, and follow-up of these patients., Methods: This report describes 2 cases of patients with treatment-refractory schizophrenia evidencing transient clozapine-induced myocarditis. Detailed information including laboratory values, imaging results, and clinical notes were gathered., Findings: The 2 cases demonstrated differing manifestations of clozapine-induced myocarditis. Both cases showed that such myocarditis can be transient and can be treated clinically with close observation without discontinuation of clozapine., Implications: These cases show that clozapine-induced myocarditis is transient at times and can self-resolve without discontinuation of clozapine. These observations may suggest a change in clinical practice so that, with close observation, we can avoid risking psychiatric decompensation in select patients with a history of treatment-resistant schizophrenia., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: Patients with bipolar disorder suffer from significant cognitive impairment that contributes directly to functional disability, yet few studies have targeted these symptoms for treatment, and the optimal study design remains unclear. We evaluated the effects of the dopamine D₂/D₃ receptor agonist pramipexole on cognition in bipolar disorder., Method: Fifty stable outpatients with DSM-IV-diagnosed bipolar I or bipolar II disorder enrolled in an 8-week, double-blind, randomized, placebo-controlled cognitive enhancement trial between July 2006 and April 2010. Patients completed neurocognitive testing at baseline and at week 8, and the primary outcome measures were change scores calculated for each of the 11 tasks. Symptoms and side effects were monitored weekly., Results: Forty-five patients completed the study (placebo, n = 24; pramipexole, n = 21), and groups were well matched on demographic and clinical features. Primary cognitive analyses indicated no compelling cognitive benefit of pramipexole versus placebo; however, secondary analyses highlight several important methodological issues for future trials and identify a subgroup of patients who might benefit more readily from cognitive enhancement strategies. This outcome suggests that the study design played a very important role in the results-implying a failed rather than altogether negative trial. Specifically, we found that even very subtle, subsyndromal mood symptoms at baseline had a significant influence on the degree of improvement due to active drug, with strictly euthymic patients faring best (multivariate analysis of variance, P = .03 in euthymic subgroup). In addition, the extent of baseline cognitive impairment also contributed to the likelihood of treatment response. Finally, concomitant medications may weaken, or in some cases enhance, response to cognitive treatment and should be accounted for in study design., Conclusions: Although our results point toward a lack of clear effect of pramipexole on cognition in bipolar patients, our data revealed a potentially beneficial effect of pramipexole in a subgroup, providing some enthusiasm for pursuing this line of research in the future. Moreover, this study emphasizes the importance of rigorous subject selection for cognitive trials in bipolar illness. Future studies will be necessary to determine the possible clinical and functional implications of these results., Trial Registration: clinicaltrials.gov Identifier: NCT00597896., (© Copyright 2012 Physicians Postgraduate Press, Inc.)

Background: There is an increased interest in early intervention strategies for severe mental disorders with hopes of mitigating the emergence and impact of the illness. Individuals at clinical high-risk (CHR) for schizophrenia have been primarily identified by the presence of attenuated positive symptoms. Although bipolar disorder and schizophrenia may have overlapping etiologies, few studies have investigated the potential prodrome in bipolar disorder. We sought to determine if there is a prodrome to bipolar disorder and if clinical or neurocognitive measures could distinguish between the bipolar and schizophrenia prodromes., Methods: We examined subjects who were initially identified as CHR for schizophrenia during the prodromal phase of the illness and followed them prospectively. Unexpectedly, eight subjects developed bipolar disorder. Baseline data from subjects who eventually developed bipolar disorder (pre-BP; N=8), schizophrenia or a psychotic disorder (pre-SZ; N=24) and a non-converter comparison group (NCC; N=115) were compared., Results: The pre-BP and pre-SZ groups did not differ on attenuated positive symptom severity, global measures of functioning or on the global neurocognitive score. Compared to NCC individuals, both pre-BP and pre-SZ patients reported more severe attenuated positive symptoms and were more likely to be on antipsychotic medication at baseline. The pre-SZ group had a significantly lower current IQ and was significantly more impaired than the NCC group on the overall neurocognitive score., Conclusions: This study provides preliminary support for a bipolar prodrome, which may be indistinguishable from the schizophrenia prodrome based on clinical and neurocognitive measures currently used in high-risk schizophrenia programs., (Copyright © 2010 Elsevier B.V. All rights reserved.)

Secretion of leptin from adipocytes communicates body energy status to the brain by activating the leptin receptor long form (LRb). LRb regulates energy homeostasis and neuroendocrine function; the absence of LRb in db/db mice results in obesity, impaired growth, infertility and diabetes. Tyr 1138 of LRb mediates activation of the transcription factor STAT3 during leptin action. To investigate the contribution of STAT3 signalling to leptin action in vivo, we replaced the gene encoding the leptin receptor (lepr) in mice with an allele coding for a replacement of Tyr 1138 in LRb with a serine residue (lepr(S1138)) that specifically disrupts the LRb-STAT3 signal. Here we show that, like db/db mice, lepr(S1138) homozygotes (s/s) are hyperphagic and obese. However, whereas db/db mice are infertile, short and diabetic, s/s mice are fertile, long and less hyperglycaemic. Furthermore, hypothalamic expression of neuropeptide Y (NPY) is elevated in db/db mice but not s/s mice, whereas the hypothalamic melanocortin system is suppressed in both db/db and s/s mice. LRb-STAT3 signalling thus mediates the effects of leptin on melanocortin production and body energy homeostasis, whereas distinct LRb signals regulate NPY and the control of fertility, growth and glucose homeostasis.