Bio


Jacob S. Ballon, M.D., M.P.H. specializes in the treatment of people with psychotic disorders including schizophrenia. He is the Co-Director of the INSPIRE Clinic at Stanford which provides interdisciplinary care for people experiencing psychosis. He is also the co-Division Chief for General Adult Psychiatry and Psychology in the Department of Psychiatry. Dr. Ballon completed his residency at Stanford in 2009 and a Schizophrenia Research Fellowship at Columbia University in 2011.

Dr. Ballon maintains an interest in understanding the connections between the brain and the rest of the body as relates to the manifestation and treatment of people who experience psychosis. He works closely with a diverse group of researchers throughout the university and technology community to investigate these connections. He has active projects investigating the metabolic implications of schizophrenia and of psychiatric medication including the association of antipsychotic medication with weight gain and insulin resistance. He also is an active investigator in clinical trials of new medications for the treatment of schizophrenia and the associated side effects of antipsychotic mediations.

In understanding the whole-body impact of psychiatric illness, Dr. Ballon also has an active interest in the role that exercise can play in psychiatric treatment. He is the site-principal investigator of an NIMH-funded clinical trial looking at the use of aerobic exercise to improve cognition in people with schizophrenia.

INSPIRE is an innovative interdisciplinary client-centered resource providing respectful evidence-based care to support people to achieve meaningful recovery from psychosis through collaborative partnership with individuals and their families while advancing knowledge and training for a new generation of providers. With a recovery-oriented philosophy, the clinic provides an array of services including psychopharmacology, psychotherapy, and psychosocial evaluations. As a research clinic, they are focused on collaborating with multiple disciplines throughout the university to conduct clinical and basic science research including functional imaging, clinical trials, basic pathophysiology, and genetics.

Clinical Focus


  • Psychiatry
  • psychosis
  • schizophrenia
  • early psychosis

Academic Appointments


  • Associate Professor - University Medical Line, Psychiatry and Behavioral Sciences

Administrative Appointments


  • Co-Division Chief - Division of General Adult Psychiatry and Psychology, Stanford University, Department of Psychiatry and Behavioral Sciences (2022 - Present)
  • Medical Director, H2 - Inpatient Psychiatry Unit, Stanford Hospital (2018 - 2022)
  • Co-Section Chief, Specialty Clinics Section, Stanford University, Department of Psychiatry and Behavioral Sciences (2017 - Present)
  • Co-Director, INSPIRE Clinic, Stanford University Department of Psychiatry and Behavioral Sciences (2014 - Present)
  • Chief Resident, Stanford University Department of Psychiatry and Behavioral Sciences (2008 - 2009)

Honors & Awards


  • Chairman's Award for Clinical Innovation, Stanford University, Department of Psychiatry and Behavioral Science (2016)
  • Fellow, American Psychiatric Association (2014)
  • Resident Travel Award, Clinical Trials Workshop, American Society of Clinical Psychopharmacology (2010)
  • Janssen Research Scholar, American Psychiatric Institute for Research and Education (APIRE) (2008)
  • Resident Travel Award, Clinical Trials Workshop, American Society of Clinical Psychopharmacology (2008)
  • PRITE Fellow, American College of Psychiatrists (2006-2008)
  • Resident Travel Award, Univ. of Pittsburgh, Schizophrenia Conference (2006)
  • Mark B. Fefferman, MD Memorial Award, University of California, San Diego School of Medicine (2005)

Program Affiliations


Professional Education


  • Fellowship: New York Presbyterian Columbia Dept of Psychology (2011) NY
  • M.D., University of California, San Diego (2005)
  • Residency, Stanford University, Department of Psychiatry and Behavioral Sciences (2009)
  • Schizophrenia Research Fellow, Columbia University (2011)
  • M.P.H., Columbia University, Health Policy and Management (2013)

Clinical Trials


  • A Study to Assess Efficacy and Safety of Adjunctive KarXT in Subjects With Inadequately Controlled Symptoms of Schizophrenia Recruiting

    This is a Phase 3, 6-week, randomized, double-blind, placebo-controlled, multicenter, outpatient study in subjects with schizophrenia with an inadequate response to their current atypical antipsychotic treatment. The primary objective of the study is to assess the efficacy of adjunctive KarXT (a fixed dose combination of xanomeline and trospium chloride twice daily \[BID\]) versus placebo in the treatment of subjects with inadequately controlled symptoms of schizophrenia as measured by the Positive and Negative Syndrome Scale (PANSS) Total Score.

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  • Journey Study: Evaluate the Efficacy, Safety, and Tolerability of Valbenazine as Adjunctive Treatment for Schizophrenia Recruiting

    The primary objective for this study is to evaluate the effect of adjunctive valbenazine versus placebo on symptoms of schizophrenia in participants who have inadequate response to antipsychotic treatment.

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  • A Study Evaluating the Safety, Efficacy, and Pharmacokinetics of Miricorilant in Obese Adult Patients With Schizophrenia While Taking Antipsychotic Medications (GRATITUDE II) Not Recruiting

    This Phase 2, double-blind, placebo-controlled, randomized study is to assess the safety, efficacy, and pharmacokinetics (PK) of miricorilant (CORT118335) in obese patients with schizophrenia treated with antipsychotic medications.

    Stanford is currently not accepting patients for this trial.

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  • A Study to Assess the Safety, Efficacy, and Pharmacokinetics of Miricorilant (CORT118335) in Obese Adults With Schizophrenia or Bipolar Disorder Treated With Antipsychotic Medications Not Recruiting

    This phase 2, double blind, placebo-controlled, randomized study is to assess the safety, efficacy, and pharmacokinetics (PK) of miricorilant (CORT118335) in obese adults with schizophrenia or bipolar disorder treated with antipsychotic medications.

    Stanford is currently not accepting patients for this trial.

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  • A Study to Compare Disease Progression and Modification Following Treatment With Paliperidone Palmitate Long-Acting Injection or Oral Antipsychotics in Participant's With Recent-onset Schizophrenia or Schizophreniform Not Recruiting

    The purpose of the study is to compare effectiveness of paliperidone palmitate (PP: paliperidone palmitate once-monthly and 3-month injections) versus oral antipsychotic (OAP \[that is oral paliperidone extended release {ER}, oral risperidone, or another OAP\]) in delaying time to treatment failure. The study will also evaluate changes in cognition, functioning, brain intracortical myelin (ICM) volume following treatment with PP compared with OAP in participants with recent-onset schizophrenia or schizophreniform disorder.

    Stanford is currently not accepting patients for this trial.

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  • Bromocriptine for Patients with Schizophrenia and Prediabetes Not Recruiting

    This is a multicenter open-label, pilot study to evaluate the safety and tolerability of bromocriptine, a dopamine D2/D3 receptor and serotonin 5-HT2C receptor agonist, as an adjunct to preexisting standard-of-care antipsychotic drug (APD) regimens in the management of APD-associated impaired glucose tolerance (IGT)/insulin resistance (IR). The ultimate aim of the study team is to evaluate the efficacy of bromocriptine in treating the metabolic disturbances associated with APDs and the hypothesis is that bromocriptine will be a well-tolerated, safe, and inexpensive way to ameliorate these metabolic complications and prevent or delay the onset of type 2 diabetes (T2D). This study will be a small, short-duration pilot focusing on safety and tolerability. A total of 15 psychiatrically stable APD-treated adult outpatients, VA Pittsburgh , aged 18 to 65 years old, with a confirmed diagnosis of schizophrenia and comorbid IGT will be recruited and receive 6 weeks of bromocriptine (flexibly titrated, 2.5-5.0 mg PO daily). Key inclusion criteria are: 1) currently being treated with second generation APDs for 3 or more months with no change in dose in the 1 month prior to enrollment, 2) fasting glucose 100 to 125mg/dL and/or hemoglobin A1c (HbA1c) 5.7-6.4%. Key exclusions are: 1) prior APD nonadherence, 2) drug/alcohol abuse in the 3 months prior to screening, 3) a history of violent behavior/psychoses, 4) pregnancy, or 5) a diagnosis of diabetes. Subjects on other dopamine agonists or on medications that may interact with bromocriptine and those taking corticosteroids or other medications that may alter glucose levels will be excluded. The purposes of the study are to demonstrate safety/tolerability, demonstrate feasibility, provide proof of concept, and provide an open-label assessment of the metabolic and psychiatric effects of bromocriptine in patients with schizophrenia treated with APDs. The primary metabolic outcome measures will be change in IR as measured by the HOMA-IR and change in IGT measured by HbA1c. Secondary metabolic outcome measures include body weight, fasting lipids, and prolactin. The specific aims are as follows: Specific aim 1: To establish the safety and tolerability of bromocriptine in patients with schizophrenia and IGT/IR treated with APDs. Specific aim 2: To demonstrate feasibility/proof of concept for an improvement in APD-induced IGT/IR with bromocriptine.

    Stanford is currently not accepting patients for this trial.

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  • CONNEX-3: A Study to Test Whether Iclepertin Improves Learning and Memory in People With Schizophrenia Not Recruiting

    This study is open to adults with schizophrenia. Schizophrenia can affect the way a person thinks, their memory and their mental functioning. Examples include struggling to remember things, or to read a book or pay attention to a movie. Some people have difficulty calculating the right change or planning a trip so that they arrive on time. The purpose of this study is to find out whether a medicine called iclepertin improves learning and memory in people with schizophrenia. Participants are put into two groups randomly, which means by chance. One group takes iclepertin tablets and the other group takes placebo tablets. Placebo tablets look like iclepertin tablets but do not contain any medicine. Participants take a tablet once a day for 26 weeks. In addition, all participants take their normal medication for schizophrenia. During this time, doctors regularly test learning and memory of the participants by use of questionnaires, interviews, and computer tests. The results of the mental ability tests are compared between the groups. Participants are in the study for about 8 months and visit the study site about 14 times. During this time, doctors regularly check participants' health and take note of any unwanted effects.

    Stanford is currently not accepting patients for this trial. For more information, please contact Daniel Virtheim, (650) 353-7030.

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  • Improving Cognition Via Exercise in Schizophrenia Not Recruiting

    People with schizophrenia display a broad range of cognitive impairments that have been identified as major determinants of poor functioning and disability. Also, people with schizophrenia are at increased risk for suicide, with approximately 40-50% of individuals attempting to take their own lives during their lifetime. The goal of the proposed study is to examine the impact of remote exercise training on cognition, suicide risk, daily functioning, and biomarkers of cognitive change and suicidality in people with schizophrenia.

    Stanford is currently not accepting patients for this trial. For more information, please contact Daniel Virtheim, 650-353-7030.

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  • Study to Evaluate the Efficacy of ALKS 3831 on Body Weight in Young Adults Who Have Been Recently Diagnosed With Schizophrenia, Schizophreniform, or Bipolar I Disorder Not Recruiting

    This study will evaluate the effect of ALKS 3831 compared to olanzapine on body weight in young adults with schizophrenia, schizophreniform, or bipolar I disorder who are early in their illness

    Stanford is currently not accepting patients for this trial. For more information, please contact Spectrum Child Health, 650-724-1175.

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  • Study to Evaluate the Efficacy, Safety, and Tolerability of Luvadaxistat in Participants With Cognitive Impairment Associated With Schizophrenia Not Recruiting

    Study to evaluate the safety and efficacy of luvadaxistat compared with placebo on improving cognitive performance in participants with schizophrenia.

    Stanford is currently not accepting patients for this trial. For more information, please contact Diane Wakeham, (650) 736- 5243.

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  • Study to Evaluate the Long-term Safety, Tolerability, and Durability of Treatment Effect of ALKS 3831 Not Recruiting

    This study will evaluate the long-term safety, tolerability, and durability of treatment effect of ALKS 3831 in subjects with schizophrenia, schizophreniform disorder, or bipolar I disorder

    Stanford is currently not accepting patients for this trial.

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2024-25 Courses


All Publications


  • Long-Term Safety, Tolerability, and Durability of Treatment Effect of Olanzapine and Samidorphan: Results of a 4-Year Open-Label Study. The Journal of clinical psychiatry Ballon, J. S., Kahn, R. S., Arevalo, C., Dunbar, M., McDonnell, D., Correll, C. U. 2024; 86 (1)

    Abstract

    Objective: Evaluate long-term safety, tolerability, and durability of the effect of olanzapine/samidorphan (OLZ/SAM) for up to 4 years in patients with schizophrenia, schizophreniform disorder, or bipolar I disorder (BD-I). Methods: This phase 3, multicenter, open-label, long-term extension (conducted June 2017-September 2023) assessed OLZ/SAM in patients completing the ENLIGHTEN clinical program. Patients received ≥2-4 years of additional treatment. Safety assessments included adverse event (AE) incidences and changes from baseline in body weight, waist circumference, and lipid/glycemic parameters. The durability of the effect was assessed using the Clinical Global Impressions-Severity (CGI-S) scale. Results: Of 524 patients enrolled, 523 received ≥1 dose of OLZ/SAM. Of these, 460 (88%) patients had schizophrenia, 15 (3%) had schizophreniform disorder, and 48 (9%) had BD-I. Mean (SD) age was 35.1 (12.2) years. Mean (SD) OLZ/SAM exposure was 652.4 (454.8) days. Of 451 patients eligible for 2 years of treatment, 242 (53.7%) received it; of 335 patients eligible for 4 years, 109 (32.5%) received it. The most common AEs were weight increased (9.8%), headache (7.1%), anxiety (6.1%), insomnia (5.9%), somnolence (5.9%), nausea (5.7%), and weight decreased (5.7%). At 2 years, mean (SD) body weight change was 0.84 (6.84) kg; waist circumference change was -0.56 (6.24) cm. At 4 years, mean (SD) body weight change was 2.65 (8.12) kg; waist circumference change was 1.37 (8.65) cm. Changes in lipid/glycemic parameters were minimal. CGI-S scores remained stable. Conclusion: OLZ/SAM maintained symptom control with a long-term safety profile over 4 years consistent with that of prior studies. Trials Registration: ClinicalTrials.gov identifier: NCT03201757.

    View details for DOI 10.4088/JCP.24m15511

    View details for PubMedID 39630083

  • Inspire self report scale (ISRS): A feasibility study of a Novel self report scale for people with schizophrenia spectrum disorders. Journal of psychiatric research Chawla, V., Bansal, N., Spelber, D., Desai, A., Frehlich, L., Ballon, J. S., Kalinowski, A., Noordsy, D. L. 2023; 165: 248-253

    Abstract

    Clinician-rated symptom scales are the current standard for outcome measures in Schizophrenia Spectrum Disorders (SSD) research. There has been growing interest in the development of self-report measures for people with SSD to support measurement-based care and inclusive research. We developed the Inspire Self Report Scale (ISRS), which measures the current magnitude of well-being, mood symptoms, psychosis, negative symptoms and cognition using 10 questions on a Likert or Visual analogue scale (VAS). The main aim of this report was to investigate the correlation and concordance between patient self-report and clinician ratings on the ISRS during a clinical encounter. When ratings were discordant, we sought to identify whether the participant's or psychiatrist's rating was more accurate. The results indicated a moderately strong statistically significant correlation between participant and clinician ratings. There was a moderate concordance between participant and clinician ratings on the ISRS. When the results were discordant, the participant ratings were assessed to be more accurate than the clinician rating over 70% of the time. The ISRS has distinct utility compared to existing scales due to the measurement of present symptom severity, capturing multiple clinical domains, and time efficiency and ease of use. Thus, it may be useful in clinical and research settings.

    View details for DOI 10.1016/j.jpsychires.2023.05.047

    View details for PubMedID 37531843

  • Reductions in synaptic marker SV2A in early-course Schizophrenia. Journal of psychiatric research Yoon, J. H., Zhang, Z., Mormino, E., Davidzon, G., Minzenberg, M. J., Ballon, J., Kalinowski, A., Hardy, K., Naganawa, M., Carson, R. E., Khalighi, M., Park, J. H., Levinson, D. F., Chin, F. T. 2023; 161: 213-217

    Abstract

    Excess synaptic pruning during neurodevelopment has emerged as one of the leading hypotheses on the causal mechanism for schizophrenia. It proposes that excess synaptic elimination occurs during development before the formal onset of illness. Accordingly, synaptic deficits may be observable at all stages of illnesses, including in the early phases. The availability of [11C]UCB-J, the first-in-human in vivo synaptic marker, represents an opportunity for testing this hypothesis with a relatively high level of precision. The first two published [11C]UCB-J schizophrenia studies have documented significant, widespread reductions in binding in chronic patients. The present study tested the hypothesis that reductions are present in early-course patients. 18 subjects completed [11C]UCB-J PET scans, (nine with schizophrenia, average duration of illness of 3.36 years, and nine demographically-matched healthy individuals). We compared binding levels, quantified as non-displaceable specific binding (BPND), in a set of a priori-specified brain regions of interest (ROIs). Eight ROIs (left and right hippocampus, right superior temporal and Heschl's gyrus, left and right putamen, and right caudal and rostral middle frontal gyrus) showed large reductions meeting Bonferroni corrected significant levels, p<0.0036. Exploratory, atlas-wide analyses confirmed widespread reductions in schizophrenia. We also observed significant positive correlations between binding levels and cognitive performance and a negative correlation with the severity of delusions. These results largely replicate findings from chronic patients, indicating that extensive [11C]UCB-J binding deficits are reliable and reproducible. Moreover, these results add to the growing evidence that excess synaptic pruning is a major disease mechanism for schizophrenia.

    View details for DOI 10.1016/j.jpsychires.2023.02.026

    View details for PubMedID 36934603

  • I THINK MY PATIENT MAY BE EXPERIENCING PSYCHOSIS - NOW WHAT? HOW PROVIDERS CAN SUPPORT EARLY IDENTIFICATION AND INTERVENTION. Eisen, K., Chari, S., Salaheldin, K., Zepp, C., Ballon, J., Hardy, K. OXFORD UNIV PRESS INC. 2022: S1
  • Increased activation product of complement 4 protein in plasma of individuals with schizophrenia. Translational psychiatry Kalinowski, A., Liliental, J., Anker, L. A., Linkovski, O., Culbertson, C., Hall, J. N., Pattni, R., Sabatti, C., Noordsy, D., Hallmayer, J. F., Mellins, E. D., Ballon, J. S., O'Hara, R., Levinson, D. F., Urban, A. E. 2021; 11 (1): 486

    Abstract

    Structural variation in the complement 4 gene (C4) confers genetic risk for schizophrenia. The variation includes numbers of the increased C4A copy number, which predicts increased C4A mRNA expression. C4-anaphylatoxin (C4-ana) is a C4 protein fragment released upon C4 protein activation that has the potential to change the blood-brain barrier (BBB). We hypothesized that elevated plasma levels of C4-ana occur in individuals with schizophrenia (iSCZ). Blood was collected from 15 iSCZ with illness duration < 5 years and from 14 healthy controls (HC). Plasma C4-ana was measured by radioimmunoassay. Other complement activation products C3-ana, C5-ana, and terminal complement complex (TCC) were also measured. Digital-droplet PCR was used to determine C4 gene structural variation state. Recombinant C4-ana was added to primary brain endothelial cells (BEC) and permeability was measured in vitro. C4-ana concentration was elevated in plasma from iSCZ compared to HC (mean=654±16ng/mL, 557±94 respectively, p=0.01). The patients also carried more copies of the C4AL gene and demonstrated a positive correlation between plasma C4-ana concentrations and C4A gene copy number. Furthermore, C4-ana increased the permeability of a monolayer of BEC in vitro. Our findings are consistent with a specific role for C4A protein in schizophrenia and raise the possibility that its activation product, C4-ana, increases BBB permeability. Exploratory analyses suggest the novel hypothesis that the relationship between C4-ana levels and C4A gene copy number could also be altered in iSCZ, suggesting an interaction with unknown genetic and/or environmental risk factors.

    View details for DOI 10.1038/s41398-021-01583-5

    View details for PubMedID 34552056

  • Cognition and Exercise: GENERAL OVERVIEW AND IMPLICATIONS FOR CARDIAC REHABILITATION. Journal of cardiopulmonary rehabilitation and prevention Gaalema, D. E., Mahoney, K., Ballon, J. S. 2021

    Abstract

    Performance of endurance exercise is associated with a broad range of cognitive benefits, with notable improvements shown across a wide variety of populations including healthy populations as well as those with impaired cognition. By examining the effects of exercise in general populations, as well in populations where cognitive deficits are pronounced, and critical to self-care, we can learn more about using exercise to ameliorate cognitive issues and apply that knowledge to other patient populations, such as those eligible for cardiac rehabilitation (CR). Cognitive challenges are a concern within CR, as management of a chronic disease is cognitively taxing, and, as expected, deficits in cognition predict worse outcomes, including lower attendance at CR. Some subsets of patients within CR may be particularly at high risk for cognitive challenges including those with heart failure with low ejection fraction, recent coronary bypass surgery, multiple chronic conditions, and patients of lower socioeconomic status. Attendance at CR is associated with cognitive gains, likely through the progressive exercise component, with larger amounts of exercise over longer periods having greater benefits. Programs should identify at-risk patients, who could gain the most from completing CR, and provide additional support to keep those patients engaged. While engaged in CR, patients should be encouraged to exercise, at least at moderate intensity, and transitioned to a long-term exercise regimen. Overall, CR programs are well-positioned to support these patients and make significant contributions to their long-term well-being.

    View details for DOI 10.1097/HCR.0000000000000644

    View details for PubMedID 34561368

  • DEVELOPING A LIVED EXPERIENCE ADVISORY COUNCIL IN AN ACADEMIC EARLY INTERVENTION FOR PSYCHOSIS CLINIC. Eisen, K., Lean, M., Ballon, J., Zepp, C., Liliental, J., Hardy, K. OXFORD UNIV PRESS INC. 2021: S140
  • Off label use of Aripiprazole shows promise as a treatment for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS): a retrospective study of 101 patients treated with a low dose of Aripiprazole. Journal of translational medicine Crosby, L. D., Kalanidhi, S., Bonilla, A., Subramanian, A., Ballon, J. S., Bonilla, H. 2021; 19 (1): 50

    View details for DOI 10.1186/s12967-021-02721-9

    View details for PubMedID 33536023

  • Roles of inflammation in intrinsic pathophysiology and antipsychotic drug-induced metabolic disturbances of schizophrenia. Behavioural brain research Prestwood, T. R., Asgariroozbehani, R. n., Wu, S. n., Agarwal, S. M., Logan, R. W., Ballon, J. S., Hahn, M. K., Freyberg, Z. n. 2021: 113101

    Abstract

    Schizophrenia is a debilitating psychiatric illness that remains poorly understood. While the bulk of symptomatology has classically been associated with disrupted brain functioning, accumulating evidence demonstrates that schizophrenia is characterized by systemic inflammation and disturbances in metabolism. Indeed, metabolic disease is a major determinant of the high mortality rate associated with schizophrenia. Antipsychotic drugs (APDs) have revolutionized management of psychosis, making it possible to rapidly control psychotic symptoms. This has ultimately reduced relapse rates of psychotic episodes and improved overall quality of life for people with schizophrenia. However, long-term APD use has also been associated with significant metabolic disturbances including weight gain, dysglycemia, and worsening of the underlying cardiometabolic disease intrinsic to schizophrenia. While the mechanisms for these intrinsic and medication-induced metabolic effects remain unclear, inflammation appears to play a key role. Here, we review the evidence for roles of inflammatory mechanisms in the disease features of schizophrenia and how these mechanisms interact with APD treatment. We also discuss the effects of common inflammatory mediators on metabolic disease. Then, we review the evidence of intrinsic and APD-mediated effects on systemic inflammation in schizophrenia. Finally, we speculate about possible treatment strategies. Developing an improved understanding of inflammatory processes in schizophrenia may therefore introduce new, more effective options for treating not only schizophrenia but also primary metabolic disorders.

    View details for DOI 10.1016/j.bbr.2020.113101

    View details for PubMedID 33453341

  • Suicide Reduction in Schizophrenia via Exercise (SUnRISE): study protocol for a multi-site, single-blind, randomized clinical trial of aerobic exercise for suicide risk reduction in individuals with schizophrenia. Trials Beck-Felts, K., Goodman, M., Ospina, L. H., Wall, M., McEvoy, J., Jarskog, L. F., Ballon, J. S., Bartels, M. N., Buchsbaum, R., Sloan, R. P., Stroup, T. S., Kimhy, D. 2020; 21 (1): 871

    Abstract

    BACKGROUND: Suicide risk among individuals with schizophrenia (SZ) is intractably high, with over 40% of individuals attempting to take their own lives during their lifetime and an estimated 5-10% completing suicide. At present, available pharmacological and psychotherapeutic treatments offer limited risk reduction benefits, and thus, there remains an urgent need to explore novel interventions that will ameliorate this risk. Aerobic exercise (AE) has been shown to improve a number of predictors of suicide risk (e.g., depressed mood, sleeping difficulties). As individuals with SZ display a highly sedentary lifestyle, AE may reduce suicide risk.METHODS: Employing a multi-site, single-blind, randomized clinical trial design, we will examine the impact of AE on risk for suicide and related variables in individuals with SZ. Participants will be randomized to one of two 12-week exercise interventions: AE or a stretching and toning (ST) control intervention. Primary outcome measures will include suicide risk (Columbia Suicide Severity Rating Scale, C-SSRS) and aerobic fitness (VO2max), along with additional measures of suicide risk, mood, emotion regulation, sleep, cognition, and physical activity, with assessments completed at baseline and after 6 and 12weeks of interventions.DISCUSSION: It is hypothesized that AE will reduce suicide risk among individuals with SZ. This study may offer support for a more efficacious treatment method for this population in addition to the pre-existing pharmacological and psychotherapeutic treatment regimens.TRIAL REGISTRATION: Clinicaltrials.gov, NCT03270098 . Registered on September 1, 2017.

    View details for DOI 10.1186/s13063-020-04788-z

    View details for PubMedID 33087170

  • Ethical Issues in Schizophrenia. Focus (American Psychiatric Publishing) Beck, N. S., Ballon, J. S. 2020; 18 (4): 428–31

    View details for DOI 10.1176/appi.focus.20200030

    View details for PubMedID 33343254

  • How genome-wide association studies (GWAS) made traditional candidate gene studies obsolete NEUROPSYCHOPHARMACOLOGY Duncan, L. E., Ostacher, M., Ballon, J. 2019; 44 (9): 1518–23
  • VALIDATION OF THE NDSE, A NEW SELF REPORT SCALE FOR PEOPLE WITH PSYCHOSIS Noordsy, D., Spelber, D., Ballon, J. OXFORD UNIV PRESS. 2019: S348
  • Growth of Early Intervention in Psychosis in the United States INTERVENING EARLY IN PSYCHOSIS: A TEAM APPROACH Hardy, K. V., Ballon, J. S., Noordsy, D. L., Adelsheim, S., Hardy, K. V., Ballon, J. S., Noordsy, D. L., Adelsheim, S. 2019: 11–22
  • Improving Cognition via Exercise (ICE): Study Protocol for a Multi-Site, Parallel-Group, Single-Blind, Randomized Clinical Trial Examining the Efficacy of Aerobic Exercise to Improve Neurocognition, Daily Functioning, and Biomarkers of Cognitive Change in Individuals with Schizophrenia. Journal of psychiatry and brain science Ospina, L. H., Wall, M., Jarskog, L. F., Ballon, J. S., McEvoy, J., Bartels, M. N., Buchsbaum, R., Sloan, R. P., Stroup, T. S., Kimhy, D. 2019; 4

    Abstract

    Individuals with schizophrenia (SZ) display cognitive deficits that have been identified as major determinants of poor functioning and disability, representing a serious public health concern and an important target for interventions. At present, available treatments offer only minimal to moderate benefits to ameliorate cognitive deficits. Thus, there remains an urgent need to identify novel interventions to improve cognition in people with SZ. Emerging evidence from animal and basic human research suggests aerobic exercise training (AE) has beneficial effects on cognition. Preliminary findings suggest that AE is efficacious in improving cognitive functioning in SZ, however the extant studies have been limited by small samples, a dearth of information on biologically-relevant covariates, and limited information on impact on daily functioning. Additionally, while AE-related cognitive benefits have been linked to Brain-Derived Neurotrophic Factor (BDNF) upregulation, this putative mechanism needs confirmation. The present report describes a study protocol designed to address these limitations-we review and summarize the current literature on treatment of cognitive deficits in SZ, state the rationale for employing AE to target these deficits, and describe the current protocol-a multi-site, single-blind, randomized clinical trial aiming to recruit 200 community-dwelling individuals with SZ. Participants are randomized to one of two 12-week interventions: AE using active-play video games (i.e., Xbox Kinect) and traditional cardiovascular exercise equipment or a stretching-and-toning (ST) control intervention. Participants undergo assessments of aerobic fitness, cognition, and daily functioning, as well as BDNF and other biomarkers of cognitive change, at baseline and after 6-and 12-weeks.

    View details for DOI 10.20900/jpbs.20190020

    View details for PubMedID 31938726

  • Role of Aerobic Exercise in the Treatment of Early Psychosis INTERVENING EARLY IN PSYCHOSIS: A TEAM APPROACH Ospina, L. H., Ballon, J. S., Kimhy, D., Hardy, K. V., Ballon, J. S., Noordsy, D. L., Adelsheim, S. 2019: 265–80
  • Special Populations: College and University Students INTERVENING EARLY IN PSYCHOSIS: A TEAM APPROACH Hardy, K. V., Ballon, J. S., Chopra, M., Noordsy, D. L., Hardy, K. V., Ballon, J. S., Noordsy, D. L., Adelsheim, S. 2019: 403–15
  • Medical Workup for First-Episode Psychosis INTERVENING EARLY IN PSYCHOSIS: A TEAM APPROACH Kalinowski, A., Ballon, J. S., Hardy, K. V., Ballon, J. S., Noordsy, D. L., Adelsheim, S. 2019: 133–49
  • The Impact of Hypomania on Aerobic Capacity and Cardiopulmonary Functioning-A Case Report. Frontiers in psychiatry Shoval, A., Armstrong, H. F., Vakhrusheva, J., Ballon, J. S., Bartels, M. N., Kimhy, D. 2018; 9: 729

    Abstract

    Background: Hypomanic episodes are characterized by increased goal-directed behavior and psychomotor agitation. While the affective, cognitive, and behavioral manifestations of such episodes are well-documented, their physiological influence on aerobic capacity and cardiopulmonary functioning are unknown. Methods: We describe a case report of an individual with schizophrenia who experienced a hypomanic episode while serving as a control participant (wait list) in a single-blind, randomized clinical trial examining the impact of aerobic exercise (AE) on neurocognition in people schizophrenia. As part of the trial, participants completed two scheduled clinical assessments and cardiopulmonary exercise tests (VO2max) at baseline and 12 weeks later at end of study. All participants received standard psychiatric care during the trial. Following a baseline assessment in which he displayed no evidence of mood lability, the subject returned on Week-12 for his scheduled follow-up assessment displaying symptoms of hypomania. He was able to complete the follow-up assessment, as well as third assessment 2 weeks later (Week-14) when his hypomanic symptoms ebbed. Results: While not engaging in AE, the subject's aerobic capacity, as indexed by VO2max, increased by 33% from baseline to Week-12. In comparison, participants engaged in the aerobic exercise training increased their aerobic capacity on average by 18%. In contrast, participants in the control group displayed a small decline (-0.5%) in their VO2max scores. Moreover, the subject's aerobic capacity increased even further by Week-14 (49% increase from baseline), despite the ebbing of his hypomania symptoms at that time. These changes were accompanied by increases in markers of aerobic fitness including peak heart rate, respiratory exchange rate, peak minute ventilation, watts, and peak systolic blood pressure. Resting systolic and diastolic blood pressure, and peak diastolic blood pressure remained unchanged. Conclusions: Our findings suggest that hypomania produce substantial increase in aerobic capacity and that such elevations may remain sustained following the ebbing of hypomanic symptoms. Such elevations may be attributed to increased mobility and goal-directed behavior associated with hypomania, as individuals in hypomanic states may ambulate more frequently, for longer duration, and/or at higher intensity. Our results provide a first and unique view into the impact of hypomania on aerobic capacity and cardiopulmonary functioning.

    View details for DOI 10.3389/fpsyt.2018.00729

    View details for PubMedID 30622490

    View details for PubMedCentralID PMC6308140

  • Clozapine Titration for People in Early Psychosis A Chart Review and Treatment Guideline JOURNAL OF CLINICAL PSYCHOPHARMACOLOGY Ballon, J. S., Ashfaq, H., Noordsy, D. L. 2018; 38 (3): 234–38

    Abstract

    The use of clozapine, particularly in young people, is often limited by early treatment-emergent adverse effects including drowsiness and lethargy. Concerns about adverse effects, medication adherence, and the need for blood monitoring often impede the use of clozapine in this population, leading to repeated trials of less effective medications. Current clozapine dosing recommendations are based on people further in the course of their illness and thus reflect different responsiveness and sensitivities to antipsychotic medication. As such, there is a need for evidence-based guidelines for titration and dosing of clozapine among people in early psychosis.We performed a chart review of 14 people treated with clozapine within our early psychosis team. Data regarding dose titration, response, time to discontinuation, symptom severity, weight gain, and other adverse effects were gathered at clozapine initiation, 3 months, and last available visit on clozapine.People treated with slow titration within their first year of psychosis onset achieved sustained response at very low maintenance doses (mean dose = 81 mg/d, mean duration of treatment = 200 weeks) compared with slow titration with longer duration of illness (mean dose = 350 mg/d, mean duration of treatment = 68 weeks) or standard dose titration in early psychosis (mean dose = 112 mg/d, mean duration of treatment = 38 weeks). The most common adverse effects in all groups were weight gain and sedation, with the groups requiring higher mean doses reporting a broader range of adverse effects. There was no apparent difference in the clinical global impression for severity or improvement between the slow titration and standard titration groups in people with early psychosis. These observations are synthesized into a proposed treatment guideline for use of clozapine among people in early psychosis.We describe development of a slow titration approach to initiating clozapine among people in early psychosis. This approach resulted in clinical response at remarkably low maintenance doses of clozapine among people within their first year of illness, but not in those with longer duration of symptoms. Slow titration also led to good tolerability and acceptance of clozapine treatment for some patients.

    View details for DOI 10.1097/JCP.0000000000000860

    View details for Web of Science ID 000431001500012

    View details for PubMedID 29659460

  • Pathophysiology of drug induced weight and metabolic effects: findings from an RCT in healthy volunteers treated with olanzapine, iloperidone, or placebo JOURNAL OF PSYCHOPHARMACOLOGY Ballon, J. S., Pajvani, U. B., Mayer, L. S., Freyberg, Z., Freyberg, R., Contreras, I., Rosenbaum, M., Leibel, R. L., Lieberman, J. A. 2018; 32 (5): 533–40

    Abstract

    Second generation antipsychotics are prescribed for an increasing number of psychiatric conditions, despite variable associations with weight gain, dyslipidemia, and impaired glucose tolerance. The mechanism(s) of the apparent causal relationships between these medications and metabolic effects have been inadequately defined and are potentially confounded by genetic risk of mental illness, attendant lifestyle, and concomitant medications. Therefore, we conducted a study in which 24 healthy volunteers were randomized to olanzapine (highly weight-gain liability), iloperidone (less weight-gain liability), or placebo treatment for 28 days under double-blind conditions. We hypothesized that antipsychotics induce weight gain primarily through increased caloric intake, which causes secondary dyslipidemia and insulin resistance. Subjects were phenotyped pre- and post-treatment for body weight, adiposity by dual energy X-ray absorptiometry, energy expenditure by indirect calorimetry, food intake, oral glucose tolerance, plasma lipids, glucose, insulin, and other hormones. We found significantly increased food intake and body weight but no change in energy expenditure in olanzapine-treated subjects, with associated trends towards lipid abnormalities and insulin resistance the extent of which were presumably limited by the duration of treatment. Iloperidone treatment led to modest non-significant and placebo no weightgain, lipid increases and alterations in insulin metabolism. We conclude that second generation antipsychotic drugs, as represented by olanzapine, produce their weight and metabolic effects, predominantly, by increasing food intake which leads to weight gain that in turn induces metabolic consequences, but also through other direct effects on lipid and glucose metabolism independant of food intake and weight gain.

    View details for PubMedID 29444618

  • Therapeutic Potential of Physical Exercise in Early Psychosis. The American journal of psychiatry Noordsy, D. L., Burgess, J. D., Hardy, K. V., Yudofsky, L. M., Ballon, J. S. 2018; 175 (3): 209–14

    View details for PubMedID 29490501

  • Impact of age of onset of psychosis and engagement in higher education on duration of untreated psychosis JOURNAL OF MENTAL HEALTH Hardy, K. V., Noordsy, D. L., Ballon, J. S., McGovern, M. P., Salomon, C., Stirman, S. 2018; 27 (3): 257–62

    Abstract

    The average age of onset of psychosis coincides with the age of college enrollment. Little is known about the impact of educational engagement on DUP in a college-aged population.To determine DUP, and the impact of educational engagement, for college-aged participants of the RAISE study (n = 404).We conducted secondary data analyses on the publicly available RAISE dataset. Subsamples were analyzed to determine the impact of age and educational engagement on DUP.DUP was significantly shorter (p < 0.02) for participants who were college-aged (18-22 years, n = 44) and engaged in post-secondary education (median = 12 weeks, mean = 29 weeks) compared with participants who were college-aged and not engaged in higher education (n = 92, median = 29 weeks, mean = 44 weeks).Educational engagement appears to be associated with a shorter DUP. This may be partially explained by the presence of on-site wellness centers in college settings. However, even among young people who engaged in post-secondary education DUP was still at, or beyond, the upper limit of WHO recommendations in this group. Future research exploring how colleges could improve their capacity to detect and refer at risk students for treatment at an earlier stage is recommended.

    View details for PubMedID 29707996

  • Intrinsic and Antipsychotic Drug-Induced Metabolic Dysfunction in Schizophrenia FRONTIERS IN NEUROSCIENCE Freyberg, Z., Aslanoglou, D., Shah, R., Ballon, J. S. 2017; 11: 432

    Abstract

    For decades, there have been observations demonstrating significant metabolic disturbances in people with schizophrenia including clinically relevant weight gain, hypertension, and disturbances in glucose and lipid homeostasis. Many of these findings pre-date the use of antipsychotic drugs (APDs) which on their own are also strongly associated with metabolic side effects. The combination of APD-induced metabolic changes and common adverse environmental factors associated with schizophrenia have made it difficult to determine the specific contributions of each to the overall metabolic picture. Data from drug-naïve patients, both from the pre-APD era and more recently, suggest that there may be an intrinsic metabolic risk associated with schizophrenia. Nevertheless, these findings remain controversial due to significant clinical variability in both psychiatric and metabolic symptoms throughout patients' disease courses. Here, we provide an extensive review of classic and more recent literature describing the metabolic phenotype associated with schizophrenia. We also suggest potential mechanistic links between signaling pathways associated with schizophrenia and metabolic dysfunction. We propose that, beyond its symptomatology in the central nervous system, schizophrenia is also characterized by pathophysiology in other organ systems directly related to metabolic control.

    View details for DOI 10.3389/fnins.2017.00432

    View details for Web of Science ID 000406598400001

    View details for PubMedID 28804444

    View details for PubMedCentralID PMC5532378

  • Aerobic Exercise Training in People with Schizophrenia: Neural, Cognitive, and Functional Benefits Kimhy, D., Vakhrusheva, J., Bartels, M. N., Ballon, J. S., Castren, E., Sloan, R. P. ELSEVIER SCIENCE INC. 2017: S162–S163
  • GENETIC CORRELATION ANALYSIS OF SCHIZOPHRENIA MIRRORS KNOWN EPIDEMIOLOGICAL RELATIONSHIPS AND SUGGESTS NOVEL ASSOCIATIONS Duncan, L., Shen, H., Ballon, J. S., Hardy, K., Noordsy, D. OXFORD UNIV PRESS. 2017: S73
  • Genetic Correlation Profile of Schizophrenia Mirrors Epidemiological Results and Suggests Link Between Polygenic and Rare Variant (22q11.2) Cases of Schizophrenia. Schizophrenia bulletin Duncan, L. E., Shen, H. n., Ballon, J. S., Hardy, K. V., Noordsy, D. L., Levinson, D. F. 2017

    Abstract

    New methods in genetics research, such as linkage disequilibrium score regression (LDSR), quantify overlap in the common genetic variants that influence diverse phenotypes. It is becoming clear that genetic effects often cut across traditional diagnostic boundaries. Here, we introduce genetic correlation analysis (using LDSR) to a nongeneticist audience and report transdisciplinary discoveries about schizophrenia. This analytical study design used publically available genome wide association study (GWAS) data from approximately 1.5 million individuals. Genetic correlations between schizophrenia and 172 medical, psychiatric, personality, and metabolomic phenotypes were calculated using LDSR, as implemented in LDHub in order to identify known and new genetic correlations. Consistent with previous research, the strongest genetic correlation was with bipolar disorder. Positive genetic correlations were also found between schizophrenia and all other psychiatric phenotypes tested, the personality traits of neuroticism and openness to experience, and cigarette smoking. Novel results were found with medical phenotypes: schizophrenia was negatively genetically correlated with serum citrate, positively correlated with inflammatory bowel disease, and negatively correlated with BMI, hip, and waist circumference. The serum citrate finding provides a potential link between rare cases of schizophrenia (strongly influenced by 22q11.2 deletions) and more typical cases of schizophrenia (with polygenic influences). Overall, these genetic correlation findings match epidemiological findings, suggesting that common variant genetic effects are part of the scaffolding underlying phenotypic comorbidity. The "genetic correlation profile" is a succinct report of shared genetic effects, is easily updated with new information (eg, from future GWAS), and should become part of basic disease knowledge about schizophrenia.

    View details for PubMedID 29294133

  • Verbigeration: An overlooked symptom of a "forgotten syndrome"? Bipolar disorders Mason, D. P., Tan, M. n., Lee, J. n., Wolstencroft, P. n., Sanborn, K. n., Ballon, J. S. 2017; 19 (8): 710–12

    View details for PubMedID 29268005

  • Ultra-low dose clozapine treatment for people with early psychosis: Development of tailored treatment guidelines Noordsy, D., Ashfaq, H., Ballon, J. WILEY-BLACKWELL. 2016: 177–78
  • The impact of aerobic exercise training on cardiopulmonary functioning in individuals with schizophrenia SCHIZOPHRENIA RESEARCH Armstrong, H. F., Bartels, M. N., Paslavski, O., Cain, D., Shoval, H. A., Ballon, J. S., Khan, S., Sloan, R. P., Kimhy, D. 2016; 173 (1-2): 116–17

    View details for PubMedID 26976498

  • Aerobic exercise for cognitive deficits in schizophrenia - The impact of frequency, duration, and fidelity with target training intensity SCHIZOPHRENIA RESEARCH Kimhy, D., Lauriola, V., Bartels, M. N., Armstrong, H. F., Vakhrusheva, J., Ballon, J. S., Sloan, R. P. 2016; 172 (1-3): 213–15

    View details for PubMedID 26852401

  • Use of Active-Play Video Games to Enhance Aerobic Fitness in Schizophrenia: Feasibility, Safety, and Adherence PSYCHIATRIC SERVICES Kimhy, D., Khan, S., Ayanrouh, L., Chang, R. W., Hansen, M. C., Lister, A., Ballon, J. S., Vakhrusheva, J., Armstrong, H. F., Bartels, M. N., Sloan, R. P. 2016; 67 (2): 240-243

    Abstract

    Active-play video games have been used to enhance aerobic fitness in various clinical populations, but their use among individuals with schizophrenia has been limited.Feasibility, acceptability, safety, and adherence data were obtained for use of aerobic exercise (AE) equipment by 16 individuals with schizophrenia during a 12-week AE program consisting of three one-hour exercise sessions per week. Equipment included exercise video games for Xbox 360 with Kinect motion sensing devices and traditional exercise equipment.Most participants (81%) completed the training, attending an average of 79% of sessions. The proportion of time spent playing Xbox (39%) exceeded time spent on any other type of equipment. When using Xbox, participants played 2.24±1.59 games per session and reported high acceptability and enjoyment ratings, with no adverse events.Measures of feasibility, acceptability, adherence, and safety support the integration of active-play video games into AE training for people with schizophrenia.

    View details for DOI 10.1176/appi.ps.201400523

    View details for Web of Science ID 000377775400022

    View details for PubMedID 26423100

  • The Impact of Aerobic Exercise on Brain-Derived Neurotrophic Factor and Neurocognition in Individuals With Schizophrenia: A Single-Blind, Randomized Clinical Trial SCHIZOPHRENIA BULLETIN Kimhy, D., Vakhrusheva, J., Bartels, M. N., Armstrong, H. F., Ballon, J. S., Khan, S., Chang, R. W., Hansen, M. C., Ayanruoh, L., Lister, A., Castren, E., Smith, E. E., Sloan, R. P. 2015; 41 (4): 859-868

    Abstract

    Individuals with schizophrenia display substantial neurocognitive deficits for which available treatments offer only limited benefits. Yet, findings from studies of animals, clinical and nonclinical populations have linked neurocognitive improvements to increases in aerobic fitness (AF) via aerobic exercise training (AE). Such improvements have been attributed to up-regulation of brain-derived neurotrophic factor (BDNF). However, the impact of AE on neurocognition, and the putative role of BDNF, have not been investigated in schizophrenia. Employing a proof-of-concept, single-blind, randomized clinical trial design, 33 individuals with schizophrenia were randomized to receive standard psychiatric treatment (n = 17; "treatment as usual"; TAU) or attend a 12-week AE program (n = 16) utilizing active-play video games (Xbox 360 Kinect) and traditional AE equipment. Participants completed assessments of AF (indexed by VO2 peak ml/kg/min), neurocognition (MATRICS Consensus Cognitive Battery), and serum-BDNF before and after and 12-week period. Twenty-six participants (79%) completed the study. At follow-up, the AE participants improved their AF by 18.0% vs a -0.5% decline in the TAU group (P = .002) and improved their neurocognition by 15.1% vs -2.0% decline in the TAU group (P = .031). Hierarchical multiple regression analyses indicated that enhancement in AF and increases in BDNF predicted 25.4% and 14.6% of the neurocognitive improvement variance, respectively. The results indicate AE is effective in enhancing neurocognitive functioning in people with schizophrenia and provide preliminary support for the impact of AE-related BDNF up-regulation on neurocognition in this population. Poor AF represents a modifiable risk factor for neurocognitive dysfunction in schizophrenia for which AE training offer a safe, nonstigmatizing, and side-effect-free intervention.

    View details for DOI 10.1093/schbul/sbv022

    View details for Web of Science ID 000357891500013

    View details for PubMedID 25805886

    View details for PubMedCentralID PMC4466187

  • A SINGLE-BLIND RANDOMIZED CLINICAL TRIAL OF AEROBIC EXERCISE IN INDIVIDUALS WITH SCHIZOPHRENIA: IMPACT ON BRAIN-DERIVED NEUROTROPHIC FACTOR AND NEUROCOGNITION Kimhy, D., Vakhrusheva, J., Bartels, M. N., Armstrong, H. F., Ballon, J. S., Khan, S., Chang, R. W., Hansen, M. C., Ayanruoh, L., Lister, A. M., Rotundo, L., Castren, E., Smith, E. E., Sloan, R. P. OXFORD UNIV PRESS. 2015: S83
  • Aerobic fitness and body mass index in individuals with schizophrenia: Implications for neurocognition and daily functioning PSYCHIATRY RESEARCH Kimhy, D., Vakhrusheva, J., Bartels, M. N., Armstrong, H. E., Ballon, J. S., Khan, S., Chang, R. W., Hansen, M. C., Ayanruoh, L., Smith, E. E., Sloan, R. P. 2014; 220 (3): 784-791

    Abstract

    Previous reports indicate that among healthy individuals low aerobic fitness (AF) and high body-mass index (BMI) predict poor neurocognition and daily-functioning. It is unknown whether these associations extend to disorders characterized by poor neurocognition, such as schizophrenia. Therefore, we compared AF and BMI in individuals with schizophrenia and non-clinical controls, and then within the schizophrenia group we examined the links between AF, BMI, neurocognition and daily-functioning. Thirty-two individuals with schizophrenia and 64 gender- and age-matched controls completed assessments of AF (indexed by VO2max) and BMI. The former also completed measures of neurocognition, daily-functioning and physical activity. The schizophrenia group displayed significantly lower AF and higher BMI. In the schizophrenia group, AF was significantly correlated with overall neurocognition (r=0.57), along with executive functioning, working memory, social cognition, and processing speed. A hierarchical regression analysis indicated that AF accounted for 22% of the neurocognition variance. Furthermore, AF was significantly correlated with overall daily-functioning (r=0.46). In contrast, BMI displayed significant inverse correlations with neurocognition, but no associations to daily-functioning. AF was significantly correlated physical activity. The authors discuss the potential use of AF-enhancing interventions to improve neurocognitive and daily-functioning in schizophrenia, along with putative neurobiological mechanisms underlying these links, including Brain-Derived Neurotrophic Factor.

    View details for DOI 10.1016/j.psychres.2014.08.052

    View details for Web of Science ID 000347361300008

    View details for PubMedID 25219618

    View details for PubMedCentralID PMC4258141

  • Molecular pathophysiology of metabolic effects of antipsychotic medications TRENDS IN ENDOCRINOLOGY AND METABOLISM Ballon, J. S., Pajvani, U., Freyberg, Z., Leibel, R. L., Lieberman, J. A. 2014; 25 (11): 593-600

    Abstract

    Antipsychotic medications are associated with major metabolic changes that contribute to medical morbidity and a significantly shortened life span. The mechanisms for these changes provide us with a broader understanding of central nervous and peripheral organ-mediated metabolic regulation. This paper reviews an extensive literature regarding putative mechanisms for effects of antipsychotic medications on weight regulation and glucose homeostasis as well as potential inherent metabolic risks of schizophrenia itself. We present a model suggesting that peripheral antipsychotic targets play a critical role in drug-induced weight gain and diabetes. We propose that a better understanding of these mechanisms will be crucial to developing improved treatments for serious mental illnesses as well as providing potentially novel therapeutic targets of metabolic disorders including diabetes.

    View details for DOI 10.1016/j.tem.2014.07.004

    View details for Web of Science ID 000344514800006

    View details for PubMedID 25190097

  • Emotional granularity and social functioning in individuals with schizophrenia: An experience sampling study JOURNAL OF PSYCHIATRIC RESEARCH Kimhy, D., Vakhrusheva, J., Khan, S., Chang, R. W., Hansen, M. C., Ballon, J. S., Malaspina, D., Gross, J. J. 2014; 53: 141-148

    Abstract

    Previous research has shown that healthy individuals who fail to differentiate among emotional states (i.e., those with low emotional granularity; EG) have poorer social functioning (SF) than those with high EG. It is unknown, however, whether these associations extend to clinical disorders characterized by impaired SF, such as schizophrenia. In the present study, we compared SF and EG in individuals with schizophrenia and healthy controls, and then, within the schizophrenia group, we examined the links between EG and SF. Employing an Experience Sampling Method approach, 77 individuals with schizophrenia and 27 healthy controls rated their momentary emotions (sadness, anxiety, anger, and happiness) up to 10 times/day over a two-day period using mobile electronic devices. For each participant, we then calculated the within-subject average correlations among the momentary emotion ratings, producing two EG indices - EGIall for all emotions and EGIneg for negative ones. A subsample of participants with schizophrenia also completed self-report, interview, and ability-based measures of SF. Compared to healthy controls, individuals with schizophrenia displayed significantly poorer SF and lower EGIall, but comparable EGIneg. Within the schizophrenia group, hierarchical multiple regression analyses indicated that EGIall, but not EGIneg, significantly predicted social dysfunction after controlling for emotional awareness, symptoms, and emotional intensity and variability. Our findings indicate that individuals with schizophrenia have a relatively intact ability to differentiate among negative emotions in everyday life. However, they experience significant difficulties differentiating between positive and negative emotions, and this may contribute to their social difficulties.

    View details for DOI 10.1016/j.jpsychires.2014.01.020

    View details for PubMedID 24561000

  • Polypharmacy for schizophrenia CURRENT OPINION IN PSYCHIATRY Ballon, J., Stroup, T. S. 2013; 26 (2): 208-213

    Abstract

    Combining psychotropic medications is common for people diagnosed with schizophrenia facing a variety of clinical circumstances. This review provides an update on evidence regarding the effectiveness of polypharmacy approaches.Epidemiology studies have demonstrated that polypharmacy is extremely common, but evidence regarding all polypharmacy approaches for schizophrenia from randomized controlled trials remains scarce. Combinations of antipsychotic medicines are unsupported by evidence. Antidepressants are commonly used to treat depressive symptoms; this logical role for antidepressants has little support from randomized controlled trials (RCTs) but may be associated with lower suicide and all-cause mortality. Insufficient evidence supports the use of benzodiazepines for schizophrenia; possible risks of benzodiazepines, including increased mortality rates revealed in observational studies, warrant caution and further study.The lack of evidence regarding common treatment strategies exacerbates the tremendous challenge of providing optimal pharmacotherapy for individuals with schizophrenia. Comparative effectiveness research, using observational methods when appropriate and RCTs when possible, is needed to inform clinical practice, use resources wisely and improve outcomes.

    View details for DOI 10.1097/YCO.0b013e32835d9efb

    View details for Web of Science ID 000314397400010

    View details for PubMedID 23318662

    View details for PubMedCentralID PMC4026924

  • METFORMIN AND IMPAIRED GLUCOSE TOLERANCE IN OVERWEIGHT PERSONS WITH SCHIZOPHRENIA Ballon, J. S., Hamer, R. M., Catellier, D. J., Stewart, D., Lavange, L., Golden, L., Lieberman, J., Stroup, T., Jarskog, L. OXFORD UNIV PRESS. 2011: 24
  • Signaling pathways in schizophrenia: emerging targets and therapeutic strategies TRENDS IN PHARMACOLOGICAL SCIENCES Karam, C. S., Ballon, J. S., Bivens, N. M., Freyberg, Z., GirgiS, R. R., Lizardi-Ortiz, J. E., Markx, S., Lieberman, J. A., Javitch, J. A. 2010; 31 (8): 381-390

    Abstract

    Dopamine D(2) receptor antagonism is a unifying property of all antipsychotic drugs in use for schizophrenia. While often effective at ameliorating psychosis, these drugs are largely ineffective at treating negative and cognitive symptoms. Increasing attention is being focused on the complex genetics of the illness and the signaling pathways implicated in its pathophysiology. We review targeted approaches for pharmacotherapy involving the glutamatergic, GABAergic and cholinergic pathways. We also describe several of the major genetic findings that identify signaling pathways representing potential targets for novel pharmacological intervention. These include genes in the 22q11 locus, DISC1, Neuregulin 1/ErbB4, and components of the Akt/GSK-3 pathway.

    View details for DOI 10.1016/j.tips.2010.05.004

    View details for Web of Science ID 000281176700006

    View details for PubMedID 20579747

    View details for PubMedCentralID PMC3635536

  • Teaching Pearls from the Lost Art of Psychopharmacology JOURNAL OF PSYCHIATRIC PRACTICE Glick, I. D., Balon, R. J., Ballon, J., Rovine, D. 2009; 15 (5): 423-426

    Abstract

    Rapid advances in neuroscience and clinical research have made the practice of quality clinical psychopharmacology increasingly difficult. While practice guidelines, model psychopharmacology curricula, and clinical algorithms have helped "the science" of psychopharmacology, they often fail to provide guidance for clinicians in specific clinical situations with individual patients. Quality psychopharmacology practice is based on a combination of knowledge, experience, judgment, and luck. In this article, the authors present their collection of psychopharmacology "pearls" for trainees as well as experienced clinicians. (Journal of Psychiatric Practice 2009;15:423-426).

    View details for Web of Science ID 000270282500009

    View details for PubMedID 19820559

  • HEALTH SERVICES OUTCOMES IN VETERANS WITH SCHIZOPHRENIA AND TRAUMATIC BRAIN INJURY Ballon, J. S., Brooks, J. O., King, R., Hoblyn, J. OXFORD UNIV PRESS. 2009: 323
  • Olanzapine AMERICAN PSYCHIATRIC PUBLISHING TEXTBOOK OF PSYCHOPHARMACOLOGY, 4TH EDITION Ballon, J. S., Wirshing, D. A., Schulz, S., Schatzberg, A. F., Nemeroff, C. B. 2009: 573–98
  • Social functioning in young people at risk for schizophrenia 60th Annual Convention of the Society-of-Biological-Psychiatry Ballon, J. S., Kaur, T., Marks, I. I., Cadenhead, K. S. ELSEVIER IRELAND LTD. 2007: 29–35

    Abstract

    Deficits in social functioning are potential risk factors for schizophrenia. Social functioning was assessed in 55 individuals "at risk" for schizophrenia, 16 first episode patients with schizophrenia and 45 normal comparison subjects. The Social Adjustment Inventory for Children and Adolescents (SAICA) was administered to adolescents <18 and the Social Adjustment Scale (SAS-SR) to young adults >17. The at risk and first episode groups significantly differed from the normal subjects on measures of social functioning in the domains of peer, family, work and school relationships. Individuals at risk for schizophrenia have significant functional deficits which may be potential indicators of increased vulnerability for psychosis.

    View details for DOI 10.1016/j.psychres.2006.10.012

    View details for Web of Science ID 000247740400004

    View details for PubMedID 17383739

  • A systematic review of modafinil: Potential clinical uses and mechanisms of action JOURNAL OF CLINICAL PSYCHIATRY Ballon, J. S., Feifel, D. 2006; 67 (4): 554-566

    Abstract

    Modafinil is a novel wake-promoting agent that has U.S. Food and Drug Administration approval for narcolepsy and shift work sleep disorder and as adjunctive treatment of obstructive sleep apnea/hypopnea syndrome. Modafinil has a novel mechanism and is theorized to work in a localized manner, utilizing hypocretin, histamine, epinephrine, gamma-aminobutyric acid, and glutamate. It is a well-tolerated medication with low propensity for abuse and is frequently used for off-label indications. The objective of this study was to systematically review the available evidence supporting the clinical use of modafinil.The search term modafinil OR Provigil was searched on PubMed. Selected articles were mined for further potential sources of data. Abstracts from major scientific conferences were reviewed. Lastly, the manufacturer of modafinil in the United States was asked to provide all publications, abstracts, and unpublished data regarding studies of modafinil.There have been 33 double-blind, placebo-controlled trials of modafinil. Additionally, numerous smaller studies have been performed, and case reports of modafinil's use abound in the literature.Modafinil is a promising drug with a large potential for many uses in psychiatry and general medicine. Treating daytime sleepiness is complex, and determining the precise nature of the sleep disorder is vital. Modafinil may be an effective agent in many sleep conditions. To date, the strongest evidence among off-label uses exists for the use of modafinil in attention-deficit disorder, postanesthetic sedation, and cocaine dependence and withdrawal and as an adjunct to antidepressants for depression.

    View details for Web of Science ID 000237614100006

    View details for PubMedID 16669720

  • The effects of novel antipsychotics on glucose and lipid levels JOURNAL OF CLINICAL PSYCHIATRY Wirshing, D. A., Boyd, J. A., Meng, L. R., Ballon, J. S., Marder, S. R., Wirshing, W. C. 2002; 63 (10): 856-865

    Abstract

    The novel antipsychotics are extensively used based on their favorable extrapyramidal side effect profiles. However, accumulating evidence suggests that these agents, particularly clozapine and olanzapine, have serious side effects of their own, including weight gain and elevated glucose and triglyceride levels. The goal of this study is to compare the effects of novel antipsychotics clozapine, olanzapine, risperidone, and quetiapine and typical antipsychotics haloperidol and fluphenazine on glucose and lipid levels.The charts of 590 patients were retrospectively reviewed. Of those, 215 patients had adequate laboratory data for inclusion. Glucose and lipid level data from 2 1/2 years before and after initiation of the target antipsychotic were included. Covariates, including patients' age, the duration of antipsychotic treatment, other medications that may affect glucose or lipid levels, and the initial laboratory values, were controlled for in the analyses.Glucose levels were increased from baseline for patients treated with clozapine, olanzapine, and haloperidol. There were statistically and clinically significant differences among the medications' effects on lipid profiles (p < .05). Those receiving clozapine and olanzapine demonstrated statistically significant increases in triglyceride levels compared with the other groups. Over one third of patients treated with any of the novel antipsychotics had clinically meaningful triglyceride elevations.It has been shown that novel antipsychotics are associated with weight gain. This risk factor along with others, such as elevated glucose and triglyceride levels, compounds the risk for coronary artery disease. Routine monitoring of glucose and lipid levels during treatment with novel antipsychotics should be advocated.

    View details for Web of Science ID 000178866700002

    View details for PubMedID 12416594