Impact of different interventions on preventing suicide and suicide attempt among children and adolescents in the United States: a microsimulation model study.

Introduction: Despite considerable investment in suicide prevention since 2001, there is limited evidence for the effect of suicide prevention interventions among children and adolescents. This study aimed to estimate the potential population impact of different interventions in preventing suicide-related behaviors in children and adolescents. Methods: A microsimulation model study used data from national surveys and clinical trials to emulate the dynamic processes of developing depression and care-seeking behaviors among a US sample of children and adolescents. The simulation model examined the effect of four hypothetical suicide prevention interventions on preventing suicide and suicide attempt in children and adolescents as follows: (1) reduce untreated depression by 20, 50, and 80% through depression screening; (2) increase the proportion of acute-phase treatment completion to 90% (i.e., reduce treatment attrition); (3) suicide screening and treatment among the depressed individuals; and (4) suicide screening and treatment to 20, 50, and 80% of individuals in medical care settings. The model without any intervention simulated was the baseline. We estimated the difference in the suicide rate and risk of suicide attempts in children and adolescents between baseline and different interventions. Results: No significant reduction in the suicide rate was observed for any of the interventions. A significant decrease in the risk of suicide attempt was observed for reducing untreated depression by 80%, and for suicide screening to individuals in medical settings as follows: 20% screened: -0.68% (95% credible interval (CI): -1.05%, -0.56%), 50% screened: -1.47% (95% CI: -2.00%, -1.34%), and 80% screened: -2.14% (95% CI: -2.48%, -2.08%). Combined with 90% completion of acute-phase treatment, the risk of suicide attempt changed by -0.33% (95% CI: -0.92%, 0.04%), -0.56% (95% CI: -1.06%, -0.17%), and -0.78% (95% CI: -1.29%, -0.40%) for reducing untreated depression by 20, 50, and 80%, respectively. Combined with suicide screening and treatment among the depressed, the risk of suicide attempt changed by -0.27% (95% CI: -0.dd%, -0.16%), -0.66% (95% CI: -0.90%, -0.46%), and -0.90% (95% CI: -1.10%, -0.69%) for reducing untreated depression by 20, 50, and 80%, respectively. Conclusion: Reducing undertreatment (the untreated and dropout) of depression and suicide screening and treatment in medical care settings may be effective in preventing suicide-related behaviors in children and adolescents.

Impact of Undertreatment of Depression on Suicide Risk Among Children and Adolescents With Major Depressive Disorder: A Microsimulation Study.

Undertreatment of depression is common among children and adolescents, but evidence of the impact of undertreatment of depression on risk of suicide is limited due to the low base rate of suicide in the population and lack of sufficient data sources. We developed a microsimulation model that uses evidence from multiple sources to study the impact of different durations of antidepressant treatment on suicide risk in a synthesized sample that is nationally representative of children and adolescents with major depressive disorder. Compared with receiving no treatment, suicide rate and risk of suicide attempt both decreased with increasing duration of antidepressant treatment (for 12 weeks, suicide rate ratios = 0.78 (95% credible interval (CrI): 0.58, 1.15), 36 weeks, 0.65 (95% CrI: 0.44, 0.90), and 52 weeks, 0.63 (95% CrI: 0.45, 0.72); for suicide attempt: 12 weeks, suicide risk ratios = 0.68 (95% CrI: 0.62, 0.69), 36 weeks, 0.56 (95% CrI: 0.52, 0.57), and 52 weeks, 0.55 (95% CrI: 0.51, 0.56). The suicide rate and risk of suicide attempt were lower in children than in adolescents. Males had a lower risk of suicide attempt but higher suicide rate than females. The findings from the microsimulation model show that completion of 12-36 weeks of antidepressant treatment may reduce suicide attempt and suicide among children and adolescents with major depressive disorder.

Psychosis-Spectrum Screening and Assessment Within a College Counseling Center: A Pilot Study Exploring Feasibility and Clinical Need.

Evidence supports the use of brief psychosis-spectrum screening tools for identifying individuals at an increased risk of developing a psychotic disorder. Screening has not been well studied in general mental health settings that serve young adults in the age range associated with highest risk for psychosis. This study explored the feasibility of psychosis-risk screening and assessment among help-seeking students at a university counseling center. The PRIME Screen-Revised was administered to students at clinic intake. Participants who screened positively were offered a follow-up assessment using the Structured Interview for Psychosis-risk Syndromes (SIPS). At intake, 510 students completed the PRIME Screen-Revised, with 132 (25.9%) screening positive. Comprehensive psychosis-spectrum evaluations were completed with 38 participants, and 22 met criteria for a psychosis-spectrum disorder, representing 57.9% of this subsample. Findings suggest that psychosis-risk screening in a college clinic is a promising approach to identifying those at high risk for or in the early stages of psychosis.

Internalized stigma mediates the relation between psychosis-risk symptoms and subjective quality of life in a help-seeking sample.

Subjective quality of life can be compromised in individuals with psychosis-risk symptoms, with poorer quality of life being associated with worse functioning and later transition to psychosis. Individuals who experience psychosis-related symptoms also tend to endorse more internalized (or self-) mental health stigma when compared to controls, potentially contributing to delays in seeking treatment and increased duration of untreated psychosis, as well as interfering with treatment engagement and retention in those already receiving care. Despite these findings, and the growing recognition for prevention in earlier phases of psychotic illness, few studies have examined the relation between psychosis-risk symptoms, internalized stigma, and subjective quality of life in a younger, help-seeking sample. The present study examined whether internalized stigma mediates the relation between psychosis-risk symptoms and subjective quality of life in a transdiagnostic sample of youth (M age = 17.93, SD = 2.90) at clinical high-risk for psychosis (CHR), with early psychosis, or with non-psychotic disorders (N = 72). Psychosis-risk symptom severity was assessed using the Structured Interview for Psychosis-Risk Syndromes (SIPS). Internalized stigma was assessed using the Internalized Stigma of Mental Illness Inventory (ISMI), and subjective quality of life was assessed using the Youth Quality of Life Instrument - Short Form (YQOL-SF). Internalized stigma fully mediated the relation between psychosis-risk symptoms and subjective quality of life across the full sample (p < .05, f2 = 0.06). Findings suggest that internalized stigma may be an important target in efforts to improve quality of life for individuals in early stages of psychosis.

Race Moderates the Relation between Internalized Stigma and Suicidal Thoughts and Behaviors in Youth with Psychosis-Risk Syndromes and Early Psychosis.

Suicide is a leading cause of death among youth on the psychosis spectrum. Internalized mental health stigma is one risk factor for suicide that may be particularly salient for youth with psychosis-risk syndromes and early psychosis. Among this population, Black youth may face exposure to racism-related stressors that may exacerbate the negative effects of internalized stigma. This study examined whether internalized stigma and race interact to predict suicidal thoughts and behaviors (STB) in a help-seeking sample of Black and White adolescents with psychosis-risk syndromes and early psychosis. Findings suggest that Black youth with early psychosis spectrum disorders may be particularly vulnerable to the negative effects of internalized stigma as they pertain to STB. Internalized stigma may therefore represent an important treatment target in suicide prevention efforts among this population.

Predictors of internalized mental health stigma in a help-seeking sample of youth: The roles of psychosis-spectrum symptoms and family functioning.

Experiencing psychosis-spectrum symptoms is challenging to youth. Among many difficulties, internalized mental health stigma-the internalization of negative stereotypes-can lead to shame and withdrawal. The objective of this study was to better understand the correlates of internalized stigma among a clinical sample of youth with psychosis-spectrum symptoms. Participants (n = 66; 12-25 years old) were referred by community providers in Maryland, United States. Psychosis-spectrum symptoms were measured via the Structured Interview for Psychosis-Risk Syndromes (SIPS); family-functioning was measured via the Family Assessment Device. Interviewers rated participants' social/role functioning via the Global Functioning: Social and Role Scales. Internalized stigma was measured using the Internalized Stigma of Mental Illness (ISMI) total scale and subscales. The sample included 34 individuals at clinical high risk for psychosis, 16 experiencing early psychosis, and 16 help-seeking controls. Regression analyses indicated that unusual beliefs, avolition, role functioning, and lower family-functioning (caregiver-reported) were significantly associated with higher aspects of internalized stigma, controlling for other symptoms and sociodemographics. These models explained 27% of the variance (adjusted R2) in the total ISMI scale and between 15% to 49% of the variance in ISMI-subscales. Among this help-seeking sample, unusual beliefs, avolition, higher role functioning, and lower family-functioning (caregiver-reported) were associated with more internalized stigma. Pending future research with larger samples, therapeutic interventions focused on these factors and their correlates may benefit youth. Future research is needed to determine temporal precedence of these associations. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Relations Among Anhedonia, Reinforcement Learning, and Global Functioning in Help-seeking Youth.

Dysfunction in the neural circuits underlying salience signaling is implicated in symptoms of psychosis and may predict conversion to a psychotic disorder in youth at clinical high risk (CHR) for psychosis. Additionally, negative symptom severity, including consummatory and anticipatory aspects of anhedonia, may predict functional outcome in individuals with schizophrenia-spectrum disorders. However, it is unclear whether anhedonia is related to the ability to attribute incentive salience to stimuli (through reinforcement learning [RL]) and whether measures of anhedonia and RL predict functional outcome in a younger, help-seeking population. We administered the Salience Attribution Test (SAT) to 33 participants who met criteria for either CHR or a recent-onset psychotic disorder and 29 help-seeking youth with nonpsychotic disorders. In the SAT, participants must identify relevant and irrelevant stimulus dimensions and be sensitive to different reinforcement probabilities for the 2 levels of the relevant dimension ("adaptive salience"). Adaptive salience attribution was positively related to both consummatory pleasure and functioning in the full sample. Analyses also revealed an indirect effect of adaptive salience on the relation between consummatory pleasure and both role (αß = .22, 95% CI = 0.02, 0.48) and social functioning (αß = .14, 95% CI = 0.02, 0.30). These findings suggest a distinct pathway to poor global functioning in help-seeking youth, via impaired reward sensitivity and RL.

Evidence of reward system dysfunction in youth at clinical high-risk for psychosis from two event-related fMRI paradigms.

Abnormal reward processing is thought to play an important role in the development of psychosis, but relatively few studies have examined reward prediction errors, reinforcement learning (RL), and the reward circuitry that subserves these interconnected processes among individuals at clinical high-risk (CHR) for the disorder. Here, we present behavioral and functional neuroimaging results of two experimental tasks designed to measure overlapping aspects of reward processing among individuals at CHR (n = 22) and healthy controls (n = 19). We found no group differences in response times to positive, negative, or neutral outcome-signaling cues, and no significant differences in brain activation during reward anticipation or receipt. Youth at CHR, however, displayed clear RL impairments, as well as attenuated responses to rewards and blunted prediction error signals in the ventral striatum, dorsal anterior cingulate cortex (dACC), and ventromedial prefrontal cortex (vmPFC). Greater contrasts for cue valence (gain-loss) and outcome magnitude (large-small) in the vmPFC were associated with more severe negative symptoms, and deficits in dACC signaling during RL were associated with more depressive symptoms. Our results provide evidence for RL deficits and abnormal prediction error signaling in the brain's reward circuitry among individuals at CHR, while also suggesting that reward motivation may be relatively preserved at this stage in development. Longitudinal studies, medication-free participants, and comparison of neurobehavioral measures against both healthy and clinical controls are needed to better understand the role of reward system abnormalities in the development of psychosis.

Telepsychotherapy with Youth at Clinical High Risk for Psychosis: Clinical Issues and Best Practices during the COVID-19 Pandemic.

Early detection and prevention of psychosis has become an international priority. Much of this work has focused on youth presenting with attenuated symptoms of psychosis-those at Clinical High Risk for psychosis (CHR)-given their elevated probability of developing the full disorder in subsequent years. Individuals at CHR may be prone to exacerbated psychological distress during the COVID-19 pandemic and its subsequent physical isolation measures, due to heightened stress sensitivity and comorbid mental health problems. Telepsychotherapy holds promise for reaching this population, especially during the current COVID-19 outbreak. However, there are limited evidence-based guidelines or interventions for use of telepsychotherapy with this population. In this paper, we review common clinical issues for individuals at CHR and how they might be exacerbated by the COVID-19 pandemic; best practices for treatment and adaptations for telepsychotherapy for individuals at CHR; and highlight real clinical issues that we are currently experiencing in a United States-based specialized CHR clinic as we conduct telepsychotherapy via videoconferencing. We conclude with questions for those in the field to contemplate, as well as potential challenges and benefits in using telepsychotherapy with individuals at CHR and their families.

Evidence for Differential Predictive Performance of the Prime Screen Between Black and White Help-Seeking Youths.

OBJECTIVE: Self-report screening instruments for emerging psychosis have the potential to improve early detection efforts by increasing the number of true positives among persons deemed to be at "clinical high risk" of the disorder, but their practical utility depends on their validity across race. This study sought to examine whether a commonly used self-report screening tool for psychosis risk performed equally among black and white youths in its ability to predict clinical high-risk status. METHODS: Black (N=58) and white (N=50) help-seeking individuals ages 12-25 (61% female) were assessed with the Prime Screen and the Structured Interview for Psychosis-Risk Syndromes (SIPS). A logistic regression model estimated race differences in the strength of the relation between Prime Screen scores and SIPS-defined risk status. RESULTS: Higher Prime Screen scores significantly predicted clinical high-risk status among white (p<.01) but not black participants. Among black youths without clinical high risk, self-reported Prime Screen scores more closely resembled scores for youths (black or white) with clinical high risk than scores of white peers who were also without clinical high risk. CONCLUSIONS: Results suggest that consideration of race or ethnicity and associated cultural factors is important when screening for clinical high-risk status. Findings support the need to develop culturally valid early psychosis screening tools to promote appropriately tailored early intervention efforts.

The impact of age on the validity of psychosis-risk screening in a sample of help-seeking youth.

Self-report screening instruments offer promise in furthering early identification of at-risk youth, yet current efforts are limited by false positive rates. Identifying moderators of accuracy is a potential step towards improving identification and prevention efforts. We investigated the moderating effect of age on self-reported attenuated positive symptoms from the Prime Screen and clinician diagnosed clinical high-risk/early psychosis (CHR/EP) status. Participants (N = 134) were racially diverse, lower-income, help-seeking adolescents and young adults from a primarily urban community. The overall model predicting CHR/EP status was significant, with results suggesting the presence of a trending interaction between age and Prime Screen symptoms. Analyses indicated that number of items endorsed to predict CHR/EP decreased with age (youngest group [M = 12.99] cut off = 6 items; middle age group [M = 14.97] cut off = 3; oldest age group [M = 18.40] cut off = 1). Although younger participants endorsed more risk items on average, follow up analyses suggested that the Prime Screen was a more accurate predictor of clinician-diagnosed-risk among older participants relative to their younger peers. The current study builds on the literature identifying moderators of psychosis-risk screening measure accuracy, highlighting potential limitations of CHR/EP screening tools in younger populations.

Family functioning moderates the impact of psychosis-risk symptoms on social and role functioning.

BACKGROUND: Youth at clinical high-risk (CHR) for psychosis often experience difficulties in social and role functioning. Given evidence that family stress and support can impact psychosis-risk symptoms, as well as an individual's ability to fulfill social and role functions, family dynamics are hypothesized to moderate the effect of psychosis-risk symptoms on functioning. METHODS: Participants at CHR (N = 52) completed the clinician-administered Structured Interview for Psychosis-risk Syndromes (SIPS) and the Family Assessment Device (FAD) General Functioning Scale, a self-report measure of family functioning including cohesion and support. Interviewers rated participants' current social and role functioning using the Global Functioning: Social and Role Scales. RESULTS: Regression results indicated that positive symptoms, but not ratings of family functioning, statistically predicted social and role functioning. Perceived family functioning, however, moderated the effect of symptoms on social/role functioning. For individuals who perceived lower levels of family functioning, symptoms were moderately associated with social and role functioning (f2 = 0.17 and f2 = 0.23, respectively). In contrast, psychosis-risk symptoms were not significantly associated with social/role functioning for individuals with higher levels of perceived family functioning. Notably, positive symptoms and perceived family functioning were not associated with one another, suggesting that perceived family functioning did not directly impact symptom severity, or vice versa. CONCLUSIONS: Findings support the notion that family functioning may be a clinically meaningful factor for individuals at CHR. Although this cross-sectional data limits our discussion of potential mechanisms underlying the pattern of findings, results suggest that familial support may be beneficial for individuals at risk for psychosis.

Impact of a Care Management Entity on Use of Psychiatric Services Among Youths With Severe Mental or Behavioral Disorders.

OBJECTIVE: Care management entity models have a positive impact on functioning and symptom control among youths with serious emotional and behavioral disorders. However, little is known about whether treatment benefits are sustained after discharge. The study objective was to examine the association between enrollment in a care management entity and mental health outcomes during the year after discharge. METHODS: Data from care management entity administrative claims were linked with Medicaid claims for youths enrolled in a care management entity anytime from December 2009 through December 2013. Inverse probability treatment weighting was used to balance baseline characteristics between the youths enrolled in the care management entity and a comparison group. Study outcomes were psychiatry-related hospitalizations and emergency department (ED) visits during the year after discharge. Two models were used to compare the two groups, one modeling the probability of using any psychiatric service and one modeling the number of visits for each outcome among users of either service. RESULTS: After adjustment with inverse probability treatment weighting, 2,381 youths (care management, N=488; comparison, N=1,893) were identified. Care management was associated with a significantly lower likelihood of any psychiatry-related ED visit (odds ratio [OR]=.65, p=.017) and any psychiatric hospitalization (OR=.60, p=.011). No significant differences in outcomes were observed when the comparison was limited to users of services. CONCLUSIONS: Reduced use of psychiatric inpatient and ED services among youths enrolled in a care management entity was sustainable after discharge. Multiagency collaboration is needed to enrich the ability to assess outcomes across broader domains.

Impact of Coordinated Behavioral Health Management on Quality Measures of Antipsychotic Use.

A state Care Management Entity (CME) using the wraparound practice model provided intensive care coordination for youth with severe mental illness, those most likely to receive antipsychotics. The model has led to improved clinical/functional outcomes, but little is known about the impact on antipsychotic prescribing and safety monitoring. A pre-post study was conducted to evaluate antipsychotic dosing, concomitant antipsychotic use, and metabolic monitoring among CME-enrolled and non-CME-enrolled comparison groups. CME-enrolled youth had greater decrease in concomitant antipsychotic use than non-CME-enrolled youth, but no difference in dosing or metabolic monitoring. More education of prescribing antipsychotics and team-based engagement in care coordination are needed.

Perceived social stress and symptom severity among help-seeking adolescents with versus without clinical high-risk for psychosis.

Research suggests that social stress exposure influences illness presentation and course among youth at clinical high-risk (CHR) for psychosis, though less is known about the extent to which self-reported perceptions of social stress relate to the severity of positive symptoms. Importantly, despite the notion that youth at CHR are especially susceptible to elevations in positive symptoms under conditions of stress, no study has examined this presumption relative to other psychiatric groups. Extending previous work demonstrating that perceived social stress was higher in a CHR group than in a clinical group of non-CHR, help-seeking controls, the current study aimed to: (1) examine whether perceived social stress is related to the severity of attenuated positive symptoms in the full sample (N=110); and (2) determine whether CHR status moderates the stress-symptom relation. Exploratory analyses examined relations of perceived social stress to negative, disorganized, and general symptoms. Greater perceptions of social stress were associated with more severe positive symptoms in the entire sample; however, although positive symptoms and perceived social stress were higher in the CHR group, the strength of this relation was statistically indistinguishable across groups. No differential effect of perceived social stress was observed for any symptom domain. Results provide some support for the diathesis-stress model of psychosis, while also suggesting that social stress and symptomatology are related independent of clinical vulnerability to psychosis. Future research would benefit from longitudinal studies of stress-symptom relations across CHR and help-seeking control groups.

Prediction of outcome of bright light treatment in patients with seasonal affective disorder: Discarding the early response, confirming a higher atypical balance, and uncovering a higher body mass index at baseline as predictors of endpoint outcome.

BACKGROUND: We tested the hypothesis that the early improvement in mood after the first hour of bright light treatment compared to control dim-red light would predict the outcome at six weeks of bright light treatment for depressed mood in patients with Seasonal Affective Disorder (SAD). We also analyzed the value of Body Mass Index (BMI) and atypical symptoms of depression at baseline in predicting treatment outcome. METHODS: Seventy-eight adult participants were enrolled. The first treatment was controlled crossover, with randomized order, and included one hour of active bright light treatment and one hour of control dim-red light, with one-hour washout. Depression was measured on the Structured Interview Guide for the Hamilton Rating Scale for Depression-SAD version (SIGH-SAD). The predictive association of depression scores changes after the first session. BMI and atypical score balance with treatment outcomes at endpoint were assessed using multivariable linear and logistic regressions. RESULTS: No significant prediction by changes in depression scores after the first session was found. However, higher atypical balance scores and BMI positively predicted treatment outcome. LIMITATIONS: Absence of a control intervention for the six-weeks of treatment (only the first session in the laboratory was controlled). Exclusion of patients with comorbid substance abuse, suicidality and bipolar I disorder, and patients on antidepressant medications, reducing the generalizability of the study. CONCLUSION: Prediction of outcome by early response to light treatment was not replicated, and the previously reported prediction of baseline atypical balance was confirmed. BMI, a parameter routinely calculated in primary care, was identified as a novel predictor, and calls for replication and then exploration of possible mediating mechanisms.

Differential relations of locus of control to perceived social stress among help-seeking adolescents at low vs. high clinical risk of psychosis.

Research suggests that perceived social stress influences illness presentation and course among youth in the clinical high-risk (CHR) phase of psychosis. Little is known, however, about the social cognitive factors associated with social stress perception in this population, particularly relative to youth with non-CHR psychopathology. Individuals with psychosis tend to endorse an external locus of control (LOC), which is associated with the stress response in healthy individuals. LOC may therefore be related to perceived social stress in youth at CHR. We examined the differential relations of self-reported LOC and perceived social stress, as measured by the Behavior Assessment System for Children, Second Edition, across 45 CHR and 65 help-seeking control (HSC) participants. Youth at CHR reported more social stress (F[1, 107]=6.28, p=0.01) and a more external LOC (F[1, 107]=4.98, p=0.03) than HSCs. Further, external LOC was more strongly associated with feelings of social stress in the CHR group relative to the HSC group (interaction: b=0.35, t[105]=2.32, p<0.05, f2=0.05). Group differences in social stress, however, were nonsignificant at internal levels of LOC (b=-2.0, t[105]=-0.72, p=0.48; f2=0.00). Results suggest that perceptions of uncontrollability over one's social environment may more often induce or exacerbate feelings of stress and tension in CHR youth relative to HSCs. A better understanding of the social cognition-stress relation may improve understanding of CHR phenomenology, etiology, and treatment.

The association between sleep dysfunction and psychosis-like experiences among college students.

Sleep problems are prominent and pervasive clinical issues experienced by many people with psychotic disorders, often causing distress and functional impairment. Sleep problems are also related to psychosis-like experiences (PLE; non-diagnosable phenomenon such as transient perceptual disturbances, unusual thoughts, periodic suspiciousness) in epidemiological studies. Prior studies in this field have used brief measures that precluded the ability to test (1) whether risk for psychosis-like experiences are related to specific sub-types of sleep disturbance, and (2) whether sleep disturbance is specifically related to clinically significant (i.e., distressing) psychosis-like experiences. The current project examined the relation between specific sleep issues, and PLEs and distress associated with PLEs, in a college sample. Participants (N=420) completed the Prodromal Questionnaire-Brief (PQ-B), which assesses PLEs and associated distress, and the Iowa Sleep Disturbances Inventory - extended version (ISDI-E), which assesses thirteen separate disturbed sleep domains. Symptoms of fragmented sleep, sleep hallucinations, and night anxiety significantly correlated with PLEs, and several sleep domains were significantly associated with PLE-related distress.

Blood Levels of Monoamine Precursors and Smoking in Patients with Schizophrenia.

Smoking is highly prevalent in patients with schizophrenia and exerts a negative impact on cardiovascular mortality in these patients. Smoking has complex interactions with monoamine metabolism through the ability of cigarette smoke to suppress Type 1 T helper cell (Th1) type immunity, the immunophenotype that is implicated in phenylalanine hydroxylase (PAH) dysfunction and tryptophan (Trp) breakdown to kynurenine (Kyn) via indoleamine 2,3-dioxygenase. Nicotine also induces tyrosine hydroxylase (TH) gene expression, leading to increased synthesis of catecholamines. Furthermore, there is evidence for PAH dysfunction in schizophrenia. This study aimed to compare the plasma levels of selected monoamine precursors and their metabolites in smokers vs. non-smokers in a large sample of patients with schizophrenia. We measured plasma phenylalanine (Phe), tyrosine (Tyr), Trp, and Kyn levels using high-performance liquid chromatography and calculated Phe:Tyr and Kyn:Trp ratios in 920 patients with schizophrenia. Analysis of variance and linear regression analyses were used to compare these endpoints between three groups of patients with schizophrenia: (1) current smokers, (2) past smokers, and (3) non-smokers. There were significant differences among the three groups with regards to Tyr levels [F (2,789) = 3.77, p = 0.02], with current smokers having lower Tyr levels when compared with non-smokers (p = 0.02). Kyn levels and Kyn:Trp ratio were different among the three groups [F (2,738) = 3.17, p = 0.04, F (2,738) = 3.61, p = 0.03] with current smokers having lower Kyn levels (p = 0.04) and higher Kyn:Trp ratio (p = 0.02) when compared with past smokers. These findings need to be replicated with protocols that include healthy controls to further elucidate the neurobiological underpinnings of altered Tyr and Kyn levels in smokers. Results do suggest potential molecular links between schizophrenia and smoking that may represent biomarkers and treatment targets for reducing an important modifiable cause of general morbidity and mortality in patients with schizophrenia.