Francisco Moreno

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Scholarly Contributions

Chapters

• Garriock, H. A., & Moreno, F. A. (2011).

  Genetics of depression: Implications for clinical practice yet?

  . In Clinical Neuropsychiatry(pp 37-46.). Giovanni Fioriti Editore.
• Moreno, F. A., & Heron, S. (2010).

  Care of Underserved People with Mental Illness

  . In Treatment of the Underserved. Springer, New York, NY. doi:10.1007/978-0-387-78309-3_11
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  Before delving into a discussion about care of the uninsured and underserved mentally ill population, it is important to reflect on the historical under-representation of the field of mental health as a whole from a medical, political, social, and economic standpoint. The approach to the care of the mentally ill has been an area of debate for centuries, and the evolution of the field of mental health and substance use disorder has often lagged behind other areas of health care and social services. Following an extensive period of institutional care of the mentally ill using therapeutic asylum, a revolutionary movement came to light in the 1960s with the promise of delivering comprehensive community-based mental health services to support the de-institutionalization of the mentally ill. The Community Mental Health Movement was ethically strong and philosophically progressive, yet it was very poorly funded, and services were intermittently dispersed and fragmented. The challenge to implementation grew more daunting as a result of a drastic concurrent increase in our country’s population, an epidemic rise in drug and alcohol use disorders, and the worsening medical and social infrastructures. Communities in the United States continue to experience the unfavorable consequences of this movement, while poorly equipped criminal justice systems, and overwhelmed emergency medical and homeless services are left to deal with the results of this tragic legacy.
• Moreno, F. A., & Garriock, H. A. (2006).

  Depression and Genetics

  . In Depression: Treatment Strategies and Management.(pp 217-227.). CRC Press. doi:10.1201/B14265-12

Journals/Publications

• Howe, G. W., Cimporescu, M., Seltzer, R., Neiderhiser, J., Moreno, F., & Weihs, K. L. (2017). Combining Stress Exposure and Stress Generation: Does Neuroticism Alter the Dynamic Interplay of Stress, Depression, and Anxiety Following Job Loss?. Journal Personality, 85(4), 553-564. doi:10.1111/jopy.12260
• Ehrmann, K., Allen, J. J., & Moreno, F. A. (2021). Psilocybin for the Treatment of Obsessive-Compulsive Disorders. Current topics in behavioral neurosciences.
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  Obsessive-compulsive disorder (OCD) is a highly prevalent and disabling condition for which currently available treatments are insufficiently effective and alternatives merit priority attention. Psilocybin may represent a safe and effective avenue for treatment of individuals affected by this condition. In this chapter we briefly introduce OCD symptoms, epidemiology, as well as relevant hypotheses on the mechanism of disease that may inform treatment interventions. We briefly describe currently available treatments, mechanisms of action, and efficacy limitations, as preamble to the potential use of psilocybin and perhaps similar compounds in the treatment of OCD and related conditions. Although much is reviewed throughout this book about the mechanisms of action of psychedelic agents, a focused discussion of psilocybin effects as they pertain to OCD is also included. Our experience with incidental observation, prospective research, and current explorations of psilocybin in OCD are also described.
• Cooley, J. H., Ranjbar, N. E., Erb, M., Lee, J., Othman, M., Coppola, C. L., Moreno, F. A., Pompea, S., Berry, M. K., Duran-Cerda, D. G., Higgins, C. M., Hedlund, A., Ahner, H., Kumet, R., Heusinkveld, J., Krieg, P. A., Vercelli, D., Warren, S. M., Fonseca, J. D., , Wild, J. R., et al. (2020). Trauma-Informed Care and Cultural Humility in the Mental Health Care of People from Minoritized Communities. FOCUS, 18(1), 8-15.
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  The prevalence and impact of trauma constitute a public health crisis that is complicated by the cultural heterogeneity of contemporary society and a higher rate of trauma among individuals from minoritized communities. A trauma-informed care approach can facilitate improved treatment of those who have experienced trauma, and trauma-informed care is increasingly viewed as potentially beneficial for all patients. This article outlines general principles of trauma-informed care and ways to enact it. Because the situations in which trauma arises, the ways in which it is conceptualized, and how patients respond to it are influenced by both culture and individual factors, a cultural humility approach is also described and recommended. Psychiatrists can navigate the complex terrain of cultures and social backgrounds in the clinical encounter and can promote healing when treating patients who have experienced trauma by adopting a trauma-informed care approach and an attitude of cultural humility.
• Mendoza, N. S., Moreno, F. A., Hishaw, G. A., Saw, A. C., Fortuna, L. R., Skubel, A., Porche, M. V., Roessel, M. H., Shore, J., & Gallegos, A. (2020). Affirmative Care Across Cultures: Broadening Application. FOCUS, 18(1), 31-39.
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  Affirmative practice is an approach to health and behavioral health care that validates and supports the identities stated or expressed by those served. Affirmative care requires the practitioner to actively honor and celebrate identity while at the same time validating the oppression felt by individuals seeking services. Validation and empathy fundamentally result from increased understanding of individuals’ history, cultural context, and lived experiences. Origins of the approach honored the experience of those in LGBTQ+ communities; however, affirmative care should be valued across cultures, systems, and settings in which health and behavioral health care are offered. Affirmative care principles should be applied across cultures and communities while recognizing the worth of the individual and avoiding stereotyping. Along with delineating historical and demographic contexts, the authors offer recommendations for affirmative care in practice with African American, Asian, Indigenous, and Latinx individuals, as well as those living in rural communities.
• Moreno, F. (2020). Diversity, Equity, and Inclusion in Psychiatry. FOCUS, 18(1), 1.
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  People of the United States may debate the value and desirability of American diversity or the global and historical context contributing to national and local variations in racial, ethnic, socioeconomic, and cultural composition. However, the anticipated trajectory of this country’s increasing diversity, as well as the inequities in social determinants, expressions of health, and experiences with health care, are well-accepted realities requiring urgent attention. Everyone experiences multiple elements of identity, which are fluid, intersecting, and essential aspects of our personhood. Given our undeniably pluralistic society, the study and practice of psychiatry requires recognizing the continuum and spectrum of differences and their impact on personal experiences, our different environments and contexts, and their complex interactions. All may influence the individual’s vulnerabilities and resilience, attribution of experiences, conceptualizations of symptoms, help seeking, and outcome expectations.This issue of Focus is dedicated to addressing diversity equity and inclusion in psychiatry. It is meant to serve as a resource to assist behavioral health providers and leaders to best understand and serve a richly diverse patient population that will invariably include individuals with backgrounds, preferences, and needs that differ from their own. Included is an introduction to the topic of diversity equity and inclusion in psychiatry (1) and various well-informed contributions on timely and relevant topics, such as the social determinants of mental health (2); strategies to increase our awareness and recruit our efforts to improve access and quality of care for individuals who are psychiatrically underserved (3); strategies to improve our sensitivity and skill to approach the care of individuals from various identity groups by incorporating principles like “affirmative care,” “trauma-informed care and cultural humility” in the service of those from minoritized communities (4, 5); and an updated critique of the DSM-5 Cultural Formulation Interview (6) and its various elements, inviting a routine integration of this tool to enhance the assessment and planning approach for all individuals.We hope this issue will also serve as a call to action to our individual and collective commitment to addressing the mental health of everyone.
• Moreno, F. A., & Chhatwal, J. (2020). Diversity and Inclusion in Psychiatry: The Pursuit of Health Equity. FOCUS, 18(1), 2-7.
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  The increasing diversity of America requires a workforce that is able to serve the mental health needs of individuals from multiple backgrounds, with a culturally proficient, inclusive, and affirming approach. To accomplish this, clinicians must be mindful of the multiple challenges presented by social determinants of mental health and access to care; the role of culture in wellness protection, mental illness expression, symptom attribution, and help seeking; the impact of provider factors, such as availability and cultural and linguistic congruence and proficiency; and the interaction of clinician and patient, who are with increasing frequency members of differing identity groups. The authors highlight the central role of clinical providers, academic institutions, and service organizations to advance health equity through training and commitment to increase high-quality services that are available, accessible, affordable, and acceptable, improving the care of all individuals.
• Moreno, F. A., Mendoza, N. S., Hishaw, G. A., Gaw, A. C., Fortuna, L. R., Skubel, A., Porche, M. V., Roessel, M. H., Shore, J., & Gallegos, A. (2020).

  Affirmative Care Across Cultures: Broadening Application

  . FOCUS, 18(1), 31-39. doi:10.1176/appi.focus.20190030
• Rubin, A., & Moreno, F. A. (2017).

  891. El Viaje al Otro Lado: Relationship between Depression Onset in Latinas and Immigration Experience Coming to the US

  . Biological Psychiatry, 81(10), S359-S360. doi:10.1016/j.biopsych.2017.02.616
• Weihs, K., Moreno, F., Howe, G. W., Cimporescu, M., Seltzer, R., & Neiderhiser, J. M. (2016).

  Combining Stress Exposure and Stress Generation: Does Neuroticism Alter the Dynamic Interplay of Stress, Depression, and Anxiety Following Job Loss?: Combining Stress Exposure

  . Journal of Personality, 85(4), 553-564. doi:10.1111/jopy.12260
• Moreno, F. A., Erickson, R. P., Garriock, H. A., Gelernter, J., Mintz, J., Oas-terpstra, J., Davies, M. A., & Delgado, P. L. (2015).

  Association Study of Genotype by Depressive Response during Tryptophan Depletion in Subjects Recovered from Major Depression.

  . Molecular neuropsychiatry, 1(3), 165-174. doi:10.1159/000439114
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  The brief and reversible mood response to acute tryptophan (TRP) depletion (ATD) is being studied as a trait marker in subjects considered at risk for major depression (MD)..ATD was administered to 64 subjects (54 European-Americans, and10 from other races) with personal and family history of MD. They were in remission and had been medication-free for at least three months. Subjects received an active and sham condition in a random assignment, double-blind crossover design. They were genotyped for serotonin-related candidate genes, and mood response was quantified with the Hamilton Depression Rating Scale (HDRS). Data were analyzed using Poisson regression with repeated measures and latent trajectory models..Compared to the sham control, active ATD caused modest depressive changes showing significant main effects of test condition (χ2=5.14, df=1, p=0.023) and time (χ2=12.22, df=3, p=0.007), but no significant interaction of time and test condition. Latent trajectory analysis revealed two groups, identified as depletion responders and non-responders. Those with the HTR2A rs6313 CC genotype had significantly higher HDRS scores during ATD (χ2=11.72, df=1, p=.0006)..ATD may help the identification of biological subtypes of MD. These data are consistent with imaging reports implicating 5-HT2A receptor function in ATD phenotypes.
• Moreno, F. A., Sbarra, D. A., O'connor, M. F., Moreno, F. A., & Hasselmo, K. (2015).

  Psychological distress following marital separation interacts with a polymorphism in the serotonin transporter gene to predict cardiac vagal control in the laboratory.

  . Psychophysiology, 52(6), 736-44. doi:10.1111/psyp.12409
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  Marital separation is linked to negative mental and physical health; however, the strength of this link may vary across people. This study examined changes in respiratory sinus arrhythmia (RSA), used to assess cardiac vagal control, in recently separated adults (N = 79; M time since separation = 3.5 months). When reflecting on the separation, self-reported psychological distress following the separation interacted with a polymorphism in the serotonin transporter gene (5-HTTLPR) and a relevant single nucleotide polymorphism (SNP), rs25531, to predict RSA. Among people reporting emotional difficulties after the separation, those who were homozygous for the short allele had lower RSA levels while reflecting on their relationship than other genotypes. The findings, although limited by the relatively small sample size, are discussed in terms of how higher-sensitivity genotypes may interact with psychological responses to stress to alter physiology.
• Aaronson, S. T., Carpenter, L. L., Conway, C. R., Reimherr, F. W., Lisanby, S. H., Schwartz, T. L., Moreno, F. A., Dunner, D. L., Lesem, M. D., Thompson, P. M., Vine, C. J., Banov, M. D., Bernstein, L. P., Lehman, R. B., Brannon, G. E., Keepers, G. A., O'reardon, J. P., Rudolph, R. L., Bunker, M., & Husain, M. M. (2013).

  Vagus nerve stimulation therapy randomized to different amounts of electrical charge for treatment-resistant depression: acute and chronic effects.

  . Brain stimulation, 6(4), 631-40. doi:10.1016/j.brs.2012.09.013
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  Major depressive disorder is a prevalent, disabling, and often chronic or recurrent psychiatric condition. About 35% of patients fail to respond to conventional treatment approaches and are considered to have treatment-resistant depression (TRD)..We compared the safety and effectiveness of different stimulation levels of adjunctive vagus nerve stimulation (VNS) therapy for the treatment of TRD..In a multicenter, double blind study, 331 patients with TRD were randomized to one of three dose groups: LOW (0.25 mA current, 130 μs pulse width), MEDIUM (0.5-1.0 mA, 250 μs), or HIGH (1.25-1.5 mA, 250 μs). A highly treatment-resistant population (>97% had failed to respond to ≥6 previous treatments) was enrolled. Response and adverse effects were assessed for 22 weeks (end of acute phase), after which output current could be increased, if clinically warranted. Assessments then continued until Week 50 (end of long-term phase)..VNS therapy was well tolerated. During the acute phase, all groups showed statistically significant improvement on the primary efficacy endpoint (change in Inventory of Depressive Symptomatology-Clinician Administered Version [IDS-C]), but not for any between-treatment group comparisons. In the long-term phase, mean change in IDS-C scores showed continued improvement. Post-hoc analyses demonstrated a statistically significant correlation between total charge delivered per day and decreasing depressive symptoms; and analysis of acute phase responders demonstrated significantly greater durability of response at MEDIUM and HIGH doses than at the LOW dose..TRD patients who received adjunctive VNS showed significant improvement at study endpoint compared with baseline, and the effect was durable over 1 year. Higher electrical dose parameters were associated with response durability.
• Chong, J., & Moreno, F. A. (2012).

  Feasibility and acceptability of clinic-based telepsychiatry for low-income Hispanic primary care patients.

  . Telemedicine journal and e-health : the official journal of the American Telemedicine Association, 18(4), 297-304. doi:10.1089/tmj.2011.0126
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  The feasibility and acceptability of telepsychiatry for low-income Hispanic patients with major depression were assessed..In total, 167 adult Hispanic patients with major depression recruited from a community health center (CHC) were randomly assigned to receive psychiatry services through a video Webcam (WEB) (n=80) or to treatment as usual (TAU) (n=87). The WEB condition consisted of monthly telepsychiatry sessions at the CHC for 6 months provided by one of two Hispanic psychiatrists using an online virtual meeting program. TAU patients received their care from their providers. Acceptability was assessed by comparing appointment keeping for primary care versus telepsychiatry, patients' perceived working alliance with their provider, visit satisfaction, and antidepressant use. Feasibility was assessed using depression outcomes, functional days (unproductive or days lost), and whether WEB and TAU patients differed in their appointment keeping..WEB patients did not differ in the proportion of completed primary care versus telepsychiatry appointments and rated their working alliance with the psychiatrist and their visit satisfaction significantly higher than the TAU patients with their provider. Significantly more WEB than TAU patients used antidepressants. Although depression severity decreased faster among WEB than TAU patients, no differences were found in the overall depression score. WEB and TAU patients did not differ in the number of days that were lost or unproductive due to depression. Although WEB and TAU patients reported being willing to pay for mental health services provided by the CHC, almost proportionately twice as many WEB patients were willing to pay for telepsychiatry..Results show that for low-income depressed Hispanic patients, telepsychiatry service for depression is acceptable, although its feasibility is questionable. The benefits of telemedicine were discussed in terms of improving patient care in ways other than directly providing services to the patients.
• Howe, G. W., Hornberger, A. P., Neiderhiser, J. M., Weihs, K. L., & Moreno, F. A. (2012).

  Higher-order structure in the trajectories of depression and anxiety following sudden involuntary unemployment.

  . Journal of abnormal psychology, 121(2), 325-38. doi:10.1037/a0026243
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  Recent work on comorbidity finds evidence for hierarchical structure of mood and anxiety disorders and symptoms. This study tests whether a higher-order internalizing factor accounts for variation in depression and anxiety symptom severity and change over time in a sample experiencing a period of major life stress. Data on symptoms of depression, chronic worry, and social anxiety were collected five times across seven months from 426 individuals who had recently lost jobs. Growth models for each type of symptom found significant variation in individual trajectories. Slopes were highly correlated across symptom type, as were intercepts. Multilevel confirmatory factor analyses found evidence for a higher-order internalizing factor for both slopes and intercepts, reflective of comorbidity of depression and anxiety, with the internalizing factor accounting for 54% to 91% of the variance in slopes and intercepts of specific symptom sets, providing evidence for both a general common factor and domain-specific factors characterizing level and change in symptoms. Loadings on the higher order factors differed modestly for men and women, and when comparing African American and White participants, but did not differ by age, education, or history of depression. More distal factors including gender and history of depression were strongly associated with internalizing in the early weeks after job loss, but rates of change in internalizing were associated most strongly with reemployment. Findings suggest that stressors may contribute in different ways to the common internalizing factor as compared to variance in anxiety and depression that is independent of that factor.
• Moreno, F. A., Chong, J., Dumbauld, J., Humke, M., & Byreddy, S. (2012).

  Use of standard Webcam and Internet equipment for telepsychiatry treatment of depression among underserved Hispanics.

  . Psychiatric services (Washington, D.C.), 63(12), 1213-7. doi:10.1176/appi.ps.201100274
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  Depression affects nearly one in five Americans at some time in their life, causing individual suffering and financial cost. The Internet has made it possible to deliver telemedicine care economically to areas and populations with limited access to specialist or culturally and linguistically congruent care..This study compared the effectiveness for Hispanic patients of depression treatment provided by a psychiatrist through Internet videoconferencing (Webcam intervention) and treatment as usual by a primary care provider. Adults (N=167) with a diagnosis of depression were recruited from a community clinic and were randomly assigned to treatment condition. Webcam participants met remotely each month with the psychiatrist, and treatment-as-usual patients received customary care from their primary care providers, all for six months. At baseline and three and six months, analyses of variance tested differences between conditions in scores on depression rating scales and quality-of-life and functional ability measures..All participants experienced an improvement in depression symptoms. Ratings on the Montgomery-Åsberg Depression Rating Scale by clinicians blind to treatment group and self-ratings on the nine-item Patient Health Questionnaire, Quality of Life Enjoyment and Satisfaction Questionnaire, and Sheehan Disability Scale showed a significant main effect of time. On all four measures, a significant interaction of time by intervention favoring the Webcam group was noted..Results suggest that telepsychiatry delivered through the Internet utilizing commercially available domestic Webcams and standard Internet and computer equipment is effective and acceptable. Use of this technology may help close the gap in access to culturally and linguistically congruent specialists.
• Olin, B., Jayewardene, A. K., Bunker, M., & Moreno, F. A. (2012).

  Mortality and suicide risk in treatment-resistant depression: an observational study of the long-term impact of intervention.

  . PloS one, 7(10), e48002. doi:10.1371/journal.pone.0048002
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  Major depressive disorder is a common global disease that causes a significant societal burden. Most interventional studies of depression provide a limited assessment of the interventions on mortality and suicide risks. This study utilizes data from an observational registry of patients with major depressive disorder to determine the impact of intervention (vagus nerve stimulation or standard pharmacological/non-pharmacological therapy) and a latent factor, patient trajectory toward response, on mortality, suicide and suicidal ideation. A total of 636 patients were available for an intent-to-treat analysis of all-cause mortality, suicide and suicidal ideation. Patients treated with vagus nerve stimulation in addition to standard therapies experienced lower, but not statistically significant, all-cause mortality (vagus nerve stimulation 4.93 per 1,000 person-years vs. 10.02 per 1,000 patient years for treatment as usual) and suicide rates (vagus nerve stimulation 0.88 per 1,000 person-years vs. 1.61 per 1,000 patient years for treatment as usual). Treatment with vagus nerve stimulation produced a statistically lower relative risk of suicidal ideation 0.80, 95% confidence interval (0.68,0.95). Further, patients that responded to either treatment saw a 51% reduction in relative risk of suicidal behavior; relative risk and 95% confidence interval of 0.49 (0.41,0.58). In summary, we find that treatment with adjunctive vagus nerve stimulation can potentially lower the risk of all-cause mortality, suicide and suicide attempts.
• Chong, J., Reinschmidt, K. M., & Moreno, F. A. (2010).

  Symptoms of depression in a Hispanic primary care population with and without chronic medical illnesses.

  . Primary care companion to the Journal of clinical psychiatry, 12(3), 0-0. doi:10.4088/pcc.09m00846blu
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  To describe somatic and psychiatric symptoms reported by Hispanic primary care patients with and without depression and/or chronic medical illnesses..Adult Hispanic patients (n = 104) in a Mobile Health Program in underserved southern Arizona participated in a survey conducted between September 2006 and February 2007 to obtain information about the somatic and psychiatric symptoms that they were experiencing. They were asked to rate the severity of their symptoms listed in the depression screen Personal Health Questionnaire-9 (PHQ-9), the Symptom Checklist-90-Revised (SCL-90-R), and 5 new symptoms described by patients in focus groups conducted in the first phase of the project. Patients were categorized as depressed if their PHQ-9 scores were 10 or above, and they were further categorized as having or not having chronic illnesses based on self-report. Analyses of variance were conducted for each SCL-90-R symptom dimension to compare across the 4 groups (group 1: not depressed and not medically ill; group 2: medically ill but not depressed; group 3: depressed but not medically ill; and group 4: depressed and medically ill)..Patients with chronic medical illnesses comorbid with depression were found to report significantly more somatic symptoms than those with only chronic medical illnesses or depression alone (P ≤ .001). They also reported significantly more psychopathology than patients with depression alone (P ≤ .05 or better)..Patients with medical illnesses comorbid with depression are more likely to exhibit psychopathology than patients with medical illnesses or depression alone.
• Oas-terpstra, J., Moreno, F. A., Frank, M. J., & Doll, B. B. (2010).

  Corrigendum: Prefrontal and striatal dopaminergic genes predict individual differences in exploration and exploitation

  . Nature Neuroscience, 13(5), 649-649. doi:10.1038/nn0510-649a
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  Corrigendum: Prefrontal and striatal dopaminergic genes predict individual differences in exploration and exploitation
• Frank, M. J., Doll, B. B., Oas-terpstra, J., & Moreno, F. A. (2009).

  Prefrontal and striatal dopaminergic genes predict individual differences in exploration and exploitation.

  . Nature neuroscience, 12(8), 1062-8. doi:10.1038/nn.2342
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  The basal ganglia support learning to exploit decisions that have yielded positive outcomes in the past. In contrast, limited evidence implicates the prefrontal cortex in the process of making strategic exploratory decisions when the magnitude of potential outcomes is unknown. Here we examine neurogenetic contributions to individual differences in these distinct aspects of motivated human behavior, using a temporal decision-making task and computational analysis. We show that two genes controlling striatal dopamine function, DARPP-32 (also called PPP1R1B) and DRD2, are associated with exploitative learning to adjust response times incrementally as a function of positive and negative decision outcomes. In contrast, a gene primarily controlling prefrontal dopamine function (COMT) is associated with a particular type of 'directed exploration', in which exploratory decisions are made in proportion to Bayesian uncertainty about whether other choices might produce outcomes that are better than the status quo. Quantitative model fits reveal that genetic factors modulate independent parameters of a reinforcement learning system.
• Moreno, F. A., Moreno, F. A., Mcknight, K. M., Demaree, H. A., Delgado, P. L., & Allen, J. J. (2009).

  Alteration of frontal EEG asymmetry during tryptophan depletion predicts future depression.

  . Journal of affective disorders, 115(1-2), 189-95. doi:10.1016/j.jad.2008.08.003
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  Tryptophan depletion (TD) reduces brain serotonin and may induce acute depressive symptomatology, especially among those with a history of Major Depression. Depressive response to TD among euthymic patients with a history of depression also predicts future depression. Better prediction might result by assessing a putative endophenotype for depressive risk, frontal electroencephalographic (EEG) asymmetry, in the context of TD..Nine euthymic history-positive participants and nine controls were administered TD. Symptomatic and EEG frontal asymmetry data were collected for 6 h following TD, and clinical status was followed for the next 12 months..The magnitude of TD-induced change in frontal EEG asymmetry significantly predicted the development of depression during the ensuing six to twelve months, and with greater sensitivity than symptomatic response..The results are tempered by the small sample size..Despite the limited sample size, these preliminary results suggest that TD-induced changes in frontal EEG asymmetry may provide a more sensitive indicator of risk for imminent depression than symptomatic response to TD.
• Carpenter, L. L., Bayat, L., Kling, M. A., Price, L. H., Tyrka, A. R., Kinkead, B., Owens, M. J., Nemeroff, C. B., & Moreno, F. A. (2008).

  Decreased cerebrospinal fluid concentrations of substance P in treatment-resistant depression and lack of alteration after acute adjunct vagus nerve stimulation therapy.

  . Psychiatry research, 157(1-3), 123-9. doi:10.1016/j.psychres.2007.04.016
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  Recent preclinical and clinical research has demonstrated that the neuropeptide substance P (SP) plays a role in the central nervous system (CNS) response to stress, and perhaps in the etiology of major depression and/or anxiety disorders. The nature of this role, however, is poorly understood. A limited body of evidence suggests that in medication-free depressed patients, cerebrospinal fluid (CSF) concentrations of SP may be elevated relative to healthy controls. Two studies have shown that antidepressant treatment does not significantly change CSF concentrations of SP. Using standard lumbar puncture techniques, baseline CSF samples were obtained from 19 medication-free healthy controls and 19 medicated patients with treatment-resistant depression (TRD). Mean CSF SP concentration was significantly lower in TRD patients on psychotropic medications than in the group of healthy subjects. After 10-12 weeks of treatment with adjunct vagus nerve stimulation (VNS), CSF SP concentrations were not significantly changed. Low CSF SP may reflect a biological marker of the subtype of severe and chronic depression that is resistant to standard therapies.
• Moreno, F. A. (2007).

  Treatment-Resistant Depression: The Role of Gene Factors

  . The Psychiatric times, 24(10), 21-24.
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  Major depressive disorder (MDD) affects a large proportion of the world's population, but much still needs to be done to categorically improve the lives of people with this condition.
• Moreno, F. A., Schnyer, R. N., Moreno, F. A., Manber, R., Hitt, S. K., Chambers, A. S., & Allen, J. J. (2007).

  Ms. Schnyer and colleagues reply [2]

  . The Journal of Clinical Psychiatry, 68(10), 1617-1618. doi:10.4088/jcp.v68n1023b
• Moreno, F. A., Yeung, A., Schnyer, R. N., Moreno, F. A., Mischoulon, D., Manber, R., Ma, Y., Hitt, S. K., Fava, M., Chambers, A. S., Alpert, J. E., & Allen, J. J. (2007).

  Acupuncture for major depressive disorder : Has its efficacy been disproved? Authors' reply

  . The Journal of Clinical Psychiatry, 68(10), 1617-1618.
• Garriock, H. A., Kling, M. A., Carpenter, L. L., Burke, W. J., Marangell, L. B., Erickson, R. P., Moreno, F. A., Schwartz, T. L., Husain, M. M., Delgado, P. L., & Burke, M. J. (2006).

  Number of risk genotypes is a risk factor for major depressive disorder: a case control study.

  . Behavioral and brain functions : BBF, 2(1), 24. doi:10.1186/1744-9081-2-24
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  The objective of the study was to determine the genetic basis of Major Depressive Disorder, and the capacity to respond to antidepressant treatment. An association study of 21 candidate polymorphisms relevant to monoamine function and the mechanism of antidepressant response was conducted in 3 phenotypically distinct samples: a group with chronic or recurrent depression unable to respond to antidepressants (non-responders) (n = 58), a group capable of symptomatic improvement with or without treatment (responders) (n = 39), and volunteer controls (n = 85). The responders and non-responders constituted a larger group of depressed subjects..A candidate gene approach was employed to asses the genetics basis of Major Depressive Disorder. The genotypic frequencies of selected polymorphisms were compared between the controls and depressed subjects. To asses the genetics basis of the capacity to respond to antidepressant treatment, the responders were compared to the non-responders. Candidate genes were chosen based on functional studies and proximity to whole genome linkage findings in the literature. Risk genotypes were identified by previous functional studies and association studies..A statistically significant difference in genotype frequency for the SLC6A4 intron 2 VNTR was detected between the subjects with a history of depression and controls (p = 0.004). Surprisingly, a statistically significant difference was detected between responders and non-responders for the DRD4 exon III VNTR genotype frequencies (p = 0.009). Furthermore, a difference between the controls and depressed subjects as well as between the controls and non-responders was detected for the number and distribution of risk genotypes in each group..An association between several monoamine-related genes and Major Depressive Disorder is supported. The data suggest that the two depressive phenotypes are genetically different, inferring that the genetic basis for the capacity to respond to standard antidepressant treatment, and the genetic susceptibility to Major Depressive Disorder may be independent. In addition, a proof of concept is provided demonstrating that the number of risk genotypes may be an indication of susceptibility of major depressive disorder and the severity of the disorder.
• Moreno, F. A., Mcgahuey, C. A., Freeman, M. P., & Delgado, P. L. (2006).

  Sex differences in depressive response during monoamine depletions in remitted depressive subjects.

  . The Journal of clinical psychiatry, 67(10), 1618-23. doi:10.4088/jcp.v67n1019
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  Although sex differences in the prevalence of depression are well known, the effects of sex on the underlying mechanisms of illness and on antidepressant action remain less clear. Tryptophan depletion and catecholamine depletion (via alpha-methylparatyrosine [AMPT] administration) are broadly utilized methods for studying the effects of the safe and transient reduction of serotonin and catecholamine neuro-transmission, respectively. The present study assessed the effects of sex on the mood response during acute monoamine depletion..Data on Hamilton Rating Scale for Depression (HAM-D) scores during depletion tests were analyzed retrospectively in 59 subjects (41 women, 18 men) who underwent tryptophan depletion and 39 subjects (25 women, 14 men) who underwent catecholamine depletion. All subjects were in remission from a DSM-IV-defined major depressive episode. Data reviewed included subjects enrolled between November 1993 and November 1997..Significant increases in HAM-D scores were observed in response to both depletion procedures, with a similar magnitude of change. Analysis of variance with repeated measures of HAM-D scores revealed a significant main effect of time for tryptophan depletion (F = 7.31, df = 3, p < .01) and for catecholamine depletion (F = 9.61, df = 4, p < .01). Time-by-sex interaction was significant for tryptophan depletion (F = 4.04, df = 3, p = .01), but not for catecholamine depletion (F = 0.75, df = 4, p = .57). Depressive symptoms were significantly greater in women during tryptophan depletion (t test p < .01), while no significant sex differences were found during catecholamine depletion..These findings suggest that the effect of sex in depressive vulnerability may be related to differential sex effects in monoaminergic function.
• Moreno, F. A., Schnyer, R. N., Moreno, F. A., Manber, R., Hitt, S. K., Chambers, A. S., & Allen, J. J. (2006).

  Acupuncture for depression: a randomized controlled trial.

  . The Journal of clinical psychiatry, 67(11), 1665-73. doi:10.4088/jcp.v67n1101
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  To assess the efficacy of acupuncture as an intervention for major depressive disorder (MDD)..Acupuncture was examined in 151 patients with MDD (DSM-IV) who were randomly assigned to 1 of 3 groups in a double-blind randomized controlled trial. The specific intervention involved Traditional Chinese Medicine (TCM)-style acupuncture with manual stimulation for depression; the control conditions consisted of (1) a nonspecific intervention using a comparable number of legitimate acupuncture points not specifically targeted to depressive symptoms and (2) a waitlist condition, which involved waiting without intervention for 8 weeks. After 8 weeks, all patients received the depression-specific acupuncture. Each 8-week intervention regimen consisted of 12 acupuncture sessions delivered in an acupuncturist's office in the community. The primary outcome measure was the 17-item Hamilton Rating Scale for Depression. The study was conducted from February 1998 to April 2002..Twenty patients terminated treatment before the completion of the 8-week intervention (13%) but not differentially by study group. Random regression models of the intent-to-treat sample revealed that although patients receiving acupuncture improved more than those awaiting intervention, no evidence of differential efficacy of the depression-specific over nonspecific intervention was found. Response rates in acupuncture-treated patients were relatively low after 8 weeks (22% and 39% for specific and nonspecific intervention groups, respectively), with the response rate after the entire 16-week trial reaching 50%..Although TCM manual acupuncture is a well-tolerated intervention, results fail to support its efficacy as a monotherapy for MDD. It can't be ruled out that factors unique to the implementation of acupuncture in this research study may have limited the efficacy of interventions compared to those provided in naturalistic settings..ClinicalTrials.gov identifier NCT00010517.
• Moreno, F. A., Wiegand, C. B., Taitano, E. K., & Delgado, P. L. (2006).

  Safety, tolerability, and efficacy of psilocybin in 9 patients with obsessive-compulsive disorder.

  . The Journal of clinical psychiatry, 67(11), 1735-40. doi:10.4088/jcp.v67n1110
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  Anecdotal reports suggest that psychedelic agents may relieve symptoms of obsessive-compulsive disorder (OCD). This modified double-blind study investigated the safety, tolerability, and clinical effects of psilocybin, a potent 5-HT(1A) and 5-HT(2A/2C) agonist, in patients with OCD..Nine subjects with DSM-IV-defined OCD and no other current major psychiatric disorder participated in up to 4 single-dose exposures to psilocybin in doses ranging from sub-hallucinogenic to frankly hallucinogenic. Low (100 microg/kg), medium (200 microg/kg), and high (300 microg/kg) doses were assigned in that order, and a very low dose (25 microg/kg) was inserted randomly and in double-blind fashion at any time after the first dose. Testing days were separated by at least 1 week. Each session was conducted over an 8-hour period in a controlled environment in an outpatient clinic; subjects were then transferred to a psychiatric inpatient unit for overnight observation. The Yale-Brown Obsessive Compulsive Scale (YBOCS) and a visual analog scale measuring overall obsessive-compulsive symptom severity were administered at 0, 4, 8, and 24 hours post-ingestion. The Hallucinogen Rating Scale was administered at 8 hours, and vital signs were recorded at 0, 1, 4, 8, and 24 hours after ingestion. The study was conducted from November 2001 to November 2004..Nine subjects were administered a total of 29 psilocybin doses. One subject experienced transient hypertension without relation to anxiety or somatic symptoms, but no other significant adverse effects were observed. Marked decreases in OCD symptoms of variable degrees were observed in all subjects during 1 or more of the testing sessions (23%-100% decrease in YBOCS score). Repeated-measures analysis of variance for all YBOCS values revealed a significant main effect of time on Wilks lambda (F = 9.86, df = 3,3; p = .046), but no significant effect of dose (F = 2.25, df = 3,3; p = .261) or interaction of time and dose (F = 0.923, df = 9,45; p = .515). Improvement generally lasted past the 24-hour timepoint..In a controlled clinical environment, psilocybin was safely used in subjects with OCD and was associated with acute reductions in core OCD symptoms in several subjects.
• Moreno, F. A., Macey, H., & Schreiber, B. (2005).

  Carnitine levels in valproic acid-treated psychiatric patients: a cross-sectional study.

  . The Journal of clinical psychiatry, 66(5), 555-8. doi:10.4088/jcp.v66n0502
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  Carnitine facilitates the transport of long-chain fatty acids across the mitochondria for beta oxidation, and the removal of potentially toxic acylcoenzyme-A metabolites from the inner aspect of mitochondrion as acylcarnitines. Previous studies suggest a significant decrease in carnitine concentrations and changes in the ratio of acylcarnitine to free carnitine in seizure-disoriented patients treated with valproic acid (VPA), which may lead to clinical manifestations of carnitine deficiency. This study sought to explore whether the same decrease in plasma free carnitine and increase in acylcarnitines are seen when VPA is used in the treatment of patients with psychiatric disease..Thirty psychiatric patients treated with VPA for at least six months were selected for the study and granted informed consent for participation. Exclusion criteria included liver disorder or pancreatitis, metabolic defects known to affect plasma carnitine levels, or noncompliance with VPA regimen. Plasma free carnitine, total carnitine, VPA, and amylase levels were determined, and liver function tests (LFTs) were performed. Pearson correlations were conducted between VPA levels, levels and ratios of carnitines, as well as LFTs and amylase levels..Plasma free and total carnitine levels were lower than the reported normal range for the laboratory performing the assay, and the ratio of acylcarnitine to free carnitine was increased. There was a significant positive correlation of VPA levels and acylcarnitine-free carnitine ratio, a trend toward significance between VPA levels and acylcarnitine levels, and a marginal negative correlation between VPA levels and free carnitine levels. VPA levels correlated also with several LFTs and acylcarnitine levels. Octanoyl carnitine and acylcarnitine levels, as well as acylcarnitine-free carnitine and octanoyl-free carnitine ratios, correlated significantly with amylase levels..Although the study was limited by a cross-sectional design without direct control comparison, the findings suggest that patients with various psychiatric conditions treated with polypharmacy that includes VPA may have lower plasma carnitine levels than would be expected in healthy controls.
• Carpenter, L. L., Moreno, F. A., Kling, M. A., Anderson, G. M., Regenold, W. T., Labiner, D. M., & Price, L. H. (2004).

  Effect of vagus nerve stimulation on cerebrospinal fluid monoamine metabolites, norepinephrine, and gamma-aminobutyric acid concentrations in depressed patients.

  . Biological psychiatry, 56(6), 418-26. doi:10.1016/j.biopsych.2004.06.025
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  Vagus nerve stimulation (VNS) has shown promising antidepressant effects in treatment-resistant depression, but the mechanisms of action are not known. Cerebrospinal fluid (CSF) studies in epilepsy patients show that VNS alters concentrations of monamines and gamma-aminobutyric acid (GABA), neurotransmitter systems possibly involved in the pathogenesis of depression..Twenty-one adults with treatment-resistant, recurrent, or chronic major depression underwent standardized lumbar puncture for collection of 12 mL CSF on three separate but identical procedure days during participation in the VNS D-02 clinical trial. All subjects remained on stable regimens of mood medications. Collections were made at baseline (2 weeks after surgical implantation but before device activation), week 12 (end of the acute-phase study), and week 24. Cerebrospinal fluid concentrations of norepinephrine (NE), 5-hydroxyindoleacetic acid (5-HIAA), homovanillic acid (HVA), and 3-methoxy-4-hydroxyphenylglycol (MHPG) were determined with high-performance liquid chromatography. Concentrations of GABA were assayed with mass spectrometry..Comparison of sham versus active VNS revealed a significant (mean 21%) VNS-associated increase in CSF HVA. Mean CSF concentrations of NE, 5-HIAA, MHPG, and GABA did not change significantly. Higher baseline HVA/5-HIAA ratio predicted worse clinical outcome..Although several of the CSF neurochemical effects we observed in this VNS study were similar to those described in the literature for antidepressants and electroconvulsive therapy, the results do not suggest a putative antidepressant mechanism of action for VNS.
• Moreno, F. A., & Delgado, P. L. (2004).

  A genetic polymorphism within the serotonin transporter gene and response to tryptophan depletion

  . Primary psychiatry, 11(6), 49-51.
• Delgado, P. L., Moreno, F. A., Laukes, C., & Manber, R. (2002).

  Reply to Balon

  . The International Journal of Neuropsychopharmacology, 5(4), 417-417. doi:10.1017/s1461145702003139
• Moreno, F. A., Rowe, D. C., Kaiser, B., Chase, D., Michaels, T., Gelernter, J., & Delgado, P. L. (2002).

  Association between a serotonin transporter promoter region polymorphism and mood response during tryptophan depletion.

  . Molecular psychiatry, 7(2), 213-6. doi:10.1038/sj.mp.4000962
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  This study investigated the relationship between depressive symptom response during tryptophan (TRP) depletion and a functional polymorphism of the promoter region of the serotonin (5-HT) transporter gene (SLC6A4).(1) Forty-three subjects in remission from a major depressive episode who underwent TRP depletion were genotyped. DNA was extracted from blood lymphocytes or from cheek cells.(2) The two common alleles are designated long (l) and short (s). Depressive symptoms were measured with the 25-item Hamilton Depression Rating Scale (HDRS).(3) There was a significant association between the l homozygous genotype and the depressive response to TRP depletion, with a significant main effect of time (F = 8.763, df = 3, 38, P =
• Delgado, P. L., & Moreno, F. A. (2000).

  Role of norepinephrine in depression.

  . The Journal of clinical psychiatry, 61 Suppl 1(1), 5-12.
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  This article reviews the role of norepinephrine (NE) and serotonin (5-HT) in depression and the therapeutic effects of antidepressant drugs from the perspective of human neurotransmitter depletion studies. The data reviewed suggest that both noradrenergic and serotonergic systems are involved in antidepressant action, but the specific impairment that underlies depression is unclear and is likely to vary among patients. Results from neurotransmitter depletion studies in depressed patients who have responded to treatment suggest that, while interactions between NE and 5-HT are likely, neither of these 2 neurotransmitter systems is the final common pathway for the therapeutic effect of antidepressant drugs. NE-selective antidepressant drugs appear to be primarily dependent on the availability of NE for their effects. Likewise, 5-HT-selective antidepressants appear to be primarily dependent on the availability of 5-HT for their effects. Antidepressants that cause effects on both noradrenergic and serotonergic systems-such as mirtazapine-may be dependent on the availability of both neurotransmitters for their effects. Neither 5-HT nor NE depletion induced clinical depression in healthy subjects or worsened depression in unmedicated symptomatic patients with major depression. This finding suggests that the cause of depression is more complex than just an alteration in the levels of 5-HT and/or NE. For some patients, depression may be more directly caused by dysfunction in brain areas or neuronal systems modulated by monoamine systems. We propose that antidepressant drugs may enhance neurotransmission in normal noradrenergic or serotonergic neurons and, through a time-dependent but as yet undiscovered process, restore function to brain areas modulated by monoamine neurons. Future research should focus on understanding the adaptive changes that follow enhancement of synaptic levels of monoamines in neuronal circuits of the frontal cortex, amygdala, and hippocampus. Research investigating the neurobiology of depression may be more informed if the focus is shifted to investigating areas of the brain modulated by monoamine systems rather than the monoamine systems themselves.
• Gelenberg, A. J., Mcgahuey, C., Laukes, C., Okayli, G., Zentner, L., Moreno, F. A., & Delgado, P. L. (2000).

  Mirtazapine substitution in SSRI-induced sexual dysfunction.

  . The Journal of clinical psychiatry, 61(5), 356-60. doi:10.4088/jcp.v61n0506
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  Sexual side effects are a common and bothersome reaction to selective serotonin reuptake inhibitors (SSRIs), frequently leading to cessation of treatment. Mirtazapine, an alpha2-adrenoceptor and serotonin-2/3 receptor antagonist, appears to cause few sexual problems..Nineteen patients (12 women and 7 men), with SSRI-induced sexual dysfunction who were in remission from major depressive disorder (total Hamilton Rating Scale for Depression [HAM-D] score < or = 10), were switched to open-label mirtazapine for up to 6 weeks. Mirtazapine was titrated from 7.5 mg to 45 mg daily, as tolerated. Sexual functioning was measured weekly with the Arizona Sexual Experiences Scale (ASEX), and depression was measured weekly with the HAM-D..Eleven patients (58%) had a return of normal sexual functioning (mean +/- SD ASEX score = 12+/-3), and another 2 (11%) reported significant improvement in sexual functioning (mean ASEX score reduced from 24+/-1 to 20+/-0). All nineteen patients maintained their antidepressant response (HAM-D score after 6 weeks of mirtazapine = 6+/-3). The most commonly reported side effects (using moderate/severe rating on a symptom checklist) were initial sedation (N = 3), irritability (N = 6), and muscle soreness and stiffness (N = 3). Weight gain of 10 to 20 lb (4.5-9 kg) was seen in 3 patients (2 women and 1 man)..Mirtazapine is an effective antidepressant for many patients experiencing SSRI-induced sexual dysfunction.
• Mcgahuey, C. A., Gelenberg, A. J., Laukes, C. A., Moreno, F. A., Delgado, P. L., Mcknight, K. M., Manber, R., & Cin, M. T. (2000).

  The Arizona Sexual Experience Scale (ASEX): reliability and validity.

  . Journal of sex & marital therapy, 26(1), 25-40. doi:10.1080/009262300278623
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  Although sexual dysfunction is common in psychiatric patients, quantification of sexual dysfunction is limited by the paucity of validated, user-friendly scales. In order to address this problem, the authors have developed the Arizona Sexual Experiences Scale (ASEX), a five-item rating scale that quantifies sex drive, arousal, vaginal lubrication/penile erection, ability to reach orgasm, and satisfaction from orgasm. Possible total scores range from 5 to 30, with the higher scores indicating more sexual dysfunction. This study assesses the internal consistency, test-retest reliability, and convergent and discriminant validity of the ASEX.
• Moreno, F. A., & Delgado, P. L. (2000).

  Living with anxiety disorders: as good as it gets...?

  . Bulletin of the Menninger Clinic, 64(3 Suppl A), A4-21.
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  The high prevalence of anxiety disorders, along with the high rate of associated comorbidity, leads to significant financial burden and human suffering, making early detection and proper intervention a clinical priority for these conditions. Despite advances in the understanding and treatment of anxiety disorders, a number of factors diminish the likelihood that people with anxiety will benefit from these advances. The authors discuss current issues relating to the treatment of anxiety disorders. This review highlights the need for recognition of comorbid conditions, the importance of reducing the high rates of partial treatment response, the importance of being aware of the common utilization of alternative treatment interventions, and the need to recognize and treat medication-induced sexual dysfunction.
• Moreno, F. A., Heninger, G. R., Mcgahuey, C. A., & Delgado, P. L. (2000).

  Tryptophan depletion and risk of depression relapse: a prospective study of tryptophan depletion as a potential predictor of depressive episodes.

  . Biological psychiatry, 48(4), 327-9. doi:10.1016/s0006-3223(00)00893-3
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  This study investigated the relationship between depressive symptom response during tryptophan depletion and future depressive episodes..Twelve subjects with prior major depressive episodes in remission and medication-free for > or =3 months (patients), and 12 matched healthy (control) subjects received two tryptophan depletion tests 1 week apart. During follow-up the Hamilton Depression Rating Scale was administered weekly for 1 month, monthly for 3 months, and once at 6 and 12 months..With results from both tests, tryptophan depletion has a sensitivity of 78%, specificity of 80%, positive predictive value of 70%, and negative predictive value of 86% to identify future depressive episodes. Survival analysis shows that mood response to tryptophan depletion reliably predicts major depressive episodes during the follow-up year (r =.2725, p =.014)..Tryptophan depletion may be clinically useful in identifying individuals at risk for future major depressive episodes.
• Moreno, F. A., Mcgavin, C., Malan, T. P., Gelenberg, A. J., Heninger, G. R., Mathe, A. A., & Delgado, P. L. (2000).

  Tryptophan depletion selectively reduces CSF 5-HT metabolites in healthy young men: results from single lumbar puncture sampling technique.

  . The international journal of neuropsychopharmacology, 3(4), 277-283. doi:10.1017/s1461145700002133
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  Plasma tryptophan (Trp) depletion is a commonly used tool for determining the role of brain serotonin (5-HT) function in a variety of psychiatric disorders. This study measured the cerebrospinal fluid (CSF) monoamine metabolite response to Trp depletion and control testing in five healthy subjects utilizing a single lumbar puncture. Testing was done in a placebo-controlled, double-blind, randomized, cross-over design. Plasma-free and total Trp levels and behavioural ratings were obtained prior to and 5 h after ingestion of each amino-acid drink. CSF was obtained by performing a standard lumbar puncture 7 h after ingestion of the drink. Compared to control testing, Trp depletion caused a significant decrease of CSF 5-hydroxyindoleacetic acid (5-HIAA) (p = 0.03), but not of homovanillic acid or 3-methoxy-4-hydroxy-phenylglycol. Behavioural ratings were minimally affected in all subjects. This confirms that plasma Trp depletion reduces central nervous system measures of 5-HT function and suggests that the single lumbar puncture technique may be sufficient to detect the extent of CSF 5-HIAA changes during Trp depletion studies.
• Delgado, P. L., Mcgahuey, C., Moreno, F. A., Laukes, C. A., & Gelenberg, A. J. (1999).

  TREATMENT STRATEGIES FOR DEPRESSION AND SEXUAL DYSFUNCTION

  . Journal of Clinical Psychiatry, Monograph Series 17(1), 15-21.
• Moreno, F. A., & Delgado, P. L. (1999).

  Antidepressants and the brain.

  . International clinical psychopharmacology, 14 Suppl 1(3), S9-16. doi:10.1097/00004850-199905001-00003
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  The pathophysiology and effects of antidepressants in the brain are still poorly understood. While it is generally accepted that increasing the levels of monoamine in the brain is an effective way to alleviate depression, the precise neurobiological mechanisms are unclear. The evidence that monoamine function is impaired in individuals with depression is largely indirect. However, the neurotransmitter depletion model allows a more direct investigation of the role of the monoamines. In this model, tryptophan depletion is used to lower levels of serotonin and alpha-methylparatyrosine is used to induce catecholamine depletion in the brain. Studies have shown that such depletion transiently reverses antidepressant responses in the majority of patients, the response being dependent on the type of antidepressant used. However, depletion in unmedicated patients with depression did not worsen the depressive symptoms, neither did it cause depression in healthy subjects with no history of mental illness. The cause(s) of depression therefore appears to be more complex than simply a reduction in levels of monoamine or diminished function in these systems. The pathophysiology of depression may relate to dysfunction in brain areas modulated by monoamine systems. Antidepressant drugs may mediate their effects by causing adaptive changes in neurones localised in these brain areas.
• Moreno, F. A., Potter, R. L., Phillips, A. P., Moreno, F. A., Mcknight, K. M., Heninger, G. R., Gelenberg, A. J., Delgado, P. L., & Allen, J. J. (1999).

  Tryptophan depletion and depressive vulnerability.

  . Biological psychiatry, 46(4), 498-505. doi:10.1016/s0006-3223(99)00095-5
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  Rapid and transient depletion of tryptophan (TRP) causes a brief depressive relapse in most patients successfully treated with and taking selective serotonin reuptake inhibitors, but little change in drug-free, symptomatic depressed patients. This study investigates the effects of TRP depletion in drug-free subjects in clinical remission from a prior major depressive episode (MDE)..Twelve subjects with a prior MDE, currently in clinical remission and drug-free for at least 3 months (patients), and 12 healthy subjects without personal or family history of Axis I disorder (controls), received TRP depletion. The study was conducted in a double-blind, controlled [full (102-g) and quarter-strength (25 g) 15-amino acid drinks], crossover fashion. Behavioral ratings and plasma TRP levels were obtained prior to, during, and after testing..All subjects experienced significant depletion of plasma TRP on both test-drinks, showing a significant dose-response relation. Healthy control subjects had minimal mood changes, but patients had a depressive response of greater magnitude..In the context of prior TRP depletion studies with antidepressant-treated, and drug-free symptomatic depressed patients, these results suggest that depression may be caused not by an abnormality of 5-HT function, but by dysfunction of other systems or brain regions modulated by 5-HT.
• Delgado, P. L., & Moreno, F. A. (1998).

  Hallucinogens, serotonin and obsessive-compulsive disorder.

  . Journal of psychoactive drugs, 30(4), 359-66. doi:10.1080/02791072.1998.10399711
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  The serotonin (5-HT) neurotransmitter system has been implicated in the pathophysiology of several neuropsychiatric disorders, especially obsessive-compulsive disorder (OCD). Blockade of 5-HT reuptake appears to be an important initial neurobiological event in the therapeutic mechanism of action of antiobsessional drugs. However, for reasons that continue to be poorly understood, clinical improvement following initiation of treatment with 5-HT reuptake inhibitors can take up to eight to 12 weeks, and most patients do not fully improve. Recent data suggest that activation of 5-HT2A and/or 5-HT2C receptors may be important for the improvement of OCD symptoms. Most psychedelic drugs are potent agonists at 5-HT2A and 5-HT2C receptors and their binding potency to these receptors is strongly correlated with their human potency as hallucinogens. This article will briefly review the relevant clinical and preclinical studies relating to the effects of hallucinogens on OCD. These data suggest that activation of 5-HT2 receptors by hallucinogens may lead to acute reduction of, as well as possible longer-lasting beneficial effects on, the symptoms of OCD. Evidence for and against involvement of 5-HT2A and/or 5-HT2C receptors in the therapeutic effects of drug therapies for OCD are reviewed. Issues related to the pharmacological properties and safety of psychedelic drugs, when considered as potential treatments for patients with OCD, are summarized. The authors suggest that controlled trials of potent 5-HT2 agonists in people suffering from OCD are warranted.
• Delgado, P. L., Moreno, F. A., Gelenberg, A. J., & Potter, R. L. (1998).

  Sequential catecholamine and 5-HT depletion in mirtazapine-treated depressives

  . Biological Psychiatry, 43(8), S104. doi:10.1016/s0006-3223(98)90794-6
• Moreno, F. A., Gelenberg, A. J., Delgado, P. L., & Bachar, K. J. (1997).

  Pindolol augmentation of treatment-resistant depressed patients.

  . The Journal of clinical psychiatry, 58(10), 437-9. doi:10.4088/jcp.v58n1005
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  Recent uncontrolled reports describe a dramatic and rapid improvement of depressive symptoms in patients treated with the combination of pindolol and serotonin selective reuptake inhibitors or monoamine oxidase inhibitors. The present study attempts to replicate those findings..Ten outpatients with current DSM-III-R major depressive disorder who had failed to obtain or maintain an appropriate response to an adequate trial of antidepressant drug were included in a randomized double-blind, placebo-controlled, crossover study. Subjects received pindolol 2.5 mg p.o. t.i.d. or placebo for 2 weeks in addition to their current antidepressant. Clinical monitoring, vital signs, and behavioral ratings were performed weekly for the duration of the study..Pindolol was well tolerated by all patients. None of the subjects experienced significant symptom worsening during the addition of either placebo or active drug. At the end of the 2-week trial, there was no statistically significant difference between pindolol augmentation and placebo. Two patients had a categorical response during placebo treatment. No categorical responses were observed during pindolol augmentation..This study failed to replicate the rapid and dramatic response to pindolol augmentation in treatment-resistant depressed patients.
• Delgado, P. L., Gelenberg, A. J., Laukes, C., Strayer, L., & Moreno, F. A. (1996).

  Tryptophan and 5-HT in psychiatric illness.

  . Advances in experimental medicine and biology, 398, 73. doi:10.1007/978-1-4613-0381-7_9
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  Brain serotonin (5-HT) content is dependent on plasma levels of tryptophan (TRP). Rapid, transient depletion of TRP in humans can be accomplished by oral administration of a TRP-free amino acid mixture. This procedure leads to a 30 to 50% decrease in brain 5-HT levels in laboratory animals and decreases human plasma TRP levels by 70–80% in 5 hours. TRP depletion alters human behaviour in different ways depending on the gender and clinical status of the subject. This presentation will review current experience with TRP depletion in healthy subjects, depressed patients, panic disorder patients, obsessive compulsive disorder (OCD) patients, and medication-free, psychiatrically-well subjects with a prior history of major depression. TRP depletion causes a transient return of anxiety and depressive symptoms in antidepressant-treated psychiatric patients, regardless of diagnosis. In contrast, TRP depletion causes minimal change in symptoms in healthy subjects or in actively ill, medication-free patients with OCD, panic disorder or major depression. These results suggest that antidepressant drugs treat depressive and anxiety symptoms by enhancing 5-HT neurotransmission but dysfunction of the 5-HT system may not be the immediate cause of OCD, panic disorder, or major depression.

Poster Presentations

• Mora, F., Prichard, G., Aldulaimi, S., Pust, R. E., Moreno, F., Stevenson, A., & Gordon, P. R. (2017, spring). “Global Health at the University of Arizona: The Ecuador Program”. Presented by Mora F at Annual University of Arizona South Campus Graduate Medical Education Scholarly Day.. Annual University of Arizona South Campus Graduate Medical Education Scholarly Day..