Antipsychotic agents in anxiety disorders: An umbrella review.

BACKGROUND: Although not approved for the treatment of anxiety disorders (except trifluoperazine) there is ongoing off-label, unapproved use of first-generation antipsychotics (FGAs) and second-generation antipsychotics (SGAs) for anxiety disorders. There have been systematic reviews and meta-analyses on the use of antipsychotics in anxiety disorders, most of which focused on SGAs. OBJECTIVE: The specific aims of this umbrella review are to: (1) Evaluate the evidence of efficacy of FGAs and SGAs in anxiety disorders as an adjunctive treatment to traditional antidepressant treatments and other nonantipsychotic medications; (2) Compare monotherapy with antipsychotics to first-line treatments for anxiety disorders in terms of effectiveness, risks, and side effects. The review protocol is registered on PROSPERO (CRD42021237436). METHODS: An initial search was undertaken to identify systematic reviews and meta-analyses from inception until 2020, with an updated search completed August 2021 and January 2023. The searches were conducted in PubMed, MEDLINE (Ovid), EMBASE (Ovid), APA PsycInfo (Ovid), CINAHL Complete (EBSCOhost), and the Cochrane Library through hand searches of references of included articles. Review quality was measured using the AMSTAR-2 (A MeaSurement Tool to Assess Systematic Reviews) scale. RESULTS: The original and updated searches yielded 1796 and 3744 articles respectively, of which 45 were eligible. After final review, 25 systematic reviews and meta-analyses were included in the analysis. Most of the systematic reviews and meta-analyses were deemed low-quality through AMSTAR-2 with only one review being deemed high-quality. In evaluating the monotherapies with antipsychotics compared with first-line treatments for anxiety disorder there was insufficient evidence due to flawed study designs (such as problems with randomization) and small sample sizes within studies. There was limited evidence suggesting efficacy of antipsychotic agents in anxiety disorders other than quetiapine in generalized anxiety disorder (GAD). CONCLUSIONS: This umbrella review indicates a lack of high-quality studies of antipsychotics in anxiety disorders outside of the use of quetiapine in GAD. Although potentially effective for anxiety disorders, FGAs and SGAs may have risks and side effects that outweigh their efficacy, although there were limited data. Further long-term and larger-scale studies of antipsychotics in anxiety disorders are needed.

Vitamin B12 Supplementation in Psychiatric Practice.

PURPOSE OF REVIEW: Vitamin B12 (B12, cobalamin) deficiency has been associated with neuropsychiatric symptoms, suggesting a role for B12 supplementation both as a treatment for psychiatric symptoms due to B12 deficiency and as an augmentation strategy for pharmacological treatments of psychiatric disorders. This critical review discusses the major causes of B12 deficiency, the range of psychiatric and non-psychiatric manifestations of B12 deficiency, the indications for testing B12 levels, and the evidence for B12 supplementation for major psychiatric disorders. RECENT FINDINGS: We find that high-quality evidence shows no benefit to routine B12 supplementation for mild depressive symptoms or to prevent depression. There is very limited evidence on the role of B12 supplementation to augment antidepressants. No high-quality evidence to date suggests a role for routine B12 supplementation in any other major psychiatric disorder. No formal guidelines indicate when clinicians should test B12 levels for common psychiatric symptoms, in the absence of major risk factors for deficiency or cardinal symptoms of deficiency. No robust evidence currently supports routine B12 supplementation for major psychiatric disorders. However, psychiatrists should be aware of the important risk factors for B12 deficiency and should be able to identify symptoms of B12 deficiency, which requires prompt testing, medical workup, and treatment. Testing for B12 deficiency should be considered for atypical or severe psychiatric presentations.

Lifetime prevalence, comorbidities, and Sociodemographic predictors of post-traumatic stress disorder (PTSD): the National Epidemiology of Iranian Children and adolescents Psychiatric disorders (IRCAP).

OBJECTIVE: The aims of this study were to (a) evaluate the lifetime prevalence of post-traumatic stress disorder (PTSD) according to sociodemographic characteristics, (b) determine sociodemographic factors associated with PTSD, (c) estimate the lifetime prevalence rates of comorbidities by age and gender, and (d) assess the proportion of traumatic events in the non-PTSD sample and the PTSD sample, according to gender. METHODS: The data used for the present study were obtained from the IRCAP study which was a cross-sectional, community-based study on 29,250 children and adolescents aged 6-18 years from all provinces of Iran, which was done using multistage cluster sampling. Trained psychologists conducted diagnostic interviews with parents, children, and adolescents using the Persian version of the Kiddie Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version (K-SADS-PL). RESULTS: In this study, the prevalence of PTSD across the sample population was 0.6% (95% CI, 0.5-0.7%). Higher rates of PTSD were observed among girls (0.7%, CI 0.5-0.8%), adolescents aged 15-18 years (0.8%, CI 0.6-1.0%), and participants who had unemployed (1.5%, CI 0.8-2.8%), or farmer fathers (1.1%, CI 0.5-2.5%). Of the participants with PTSD, 65.1% met the criteria for at least one other psychiatric disorder. PTSD had a high rate of comorbidity with oppositional defiant disorder (22.9%, CI 17.5-29.4%), generalized anxiety disorder (20.8%, CI 15.7-27.1%), separation anxiety disorder (20.3%, CI 15.2-26.6%), and major depressive disorder (19.8%, CI 14.8-26.0%). We found 9.5% of non-PTSD sample experienced at least one traumatic event. Witness to domestic violence was the most common traumatic event experienced by 32.8% of PTSD sample. CONCLUSION: Our results in the prevalence, comorbidities, and sociodemographic factors associated with PTSD supported findings of previous studies that used a structured diagnostic interview. It is recommended to use purposive sampling and to investigate comorbidities of PTSD and type of traumatic events in a large clinical population.

Neurological manifestations as the predictors of severity and mortality in hospitalized individuals with COVID-19: a multicenter prospective clinical study.

BACKGROUNDS: The reports of neurological symptoms are increasing in cases with coronavirus disease 2019 (COVID-19). This multi-center prospective study was conducted to determine the incidence of neurological manifestations in hospitalized cases with COVID-19 and assess these symptoms as the predictors of severity and death. METHODS: Hospitalized males and females with COVID-19 who aged over 18 years were included in the study. They were examined by two neurologists at the time of admission. All survived cases were followed for 8 weeks after discharge and 16 weeks if their symptoms had no improvements. RESULTS: We included 873 participants. Of eligible cases, 122 individuals (13.97%) died during hospitalization. The most common non-neurological manifestations were fever (81.1%), cough (76.1%), fatigue (36.1%), and shortness of breath (27.6%). Aging, male gender, co-morbidity, smoking, hemoptysis, chest tightness, and shortness of breath were associated with increased odds of severe cases and/or mortality. There were 561 (64.3%) cases with smell and taste dysfunctions (hyposmia: 58.6%; anosmia: 41.4%; dysguesia: 100%). They were more common among females (69.7%) and non-smokers (66.7%). Hyposmia/anosmia and dysgeusia were found to be associated with reduced odds of severe cases and mortality. Myalgia (24.8%), headaches (12.6%), and dizziness (11.9%) were other common neurological symptoms. Headaches had negative correlation with severity and death due to COVID-19 but myalgia and dizziness were not associated. The cerebrovascular events (n = 10) and status epilepticus (n = 1) were other neurological findings. The partial or full recovery of smell and taste dysfunctions was found in 95.2% after 8 weeks and 97.3% after 16 weeks. The parosmia (30.9%) and phantosmia (9.0%) were also reported during 8 weeks of follow-up. Five cases with mild headaches and 5 cases with myalgia were reported after 16 weeks of discharge. The demyelinating myelitis (n = 1) and Guillain-Barré syndrome (n = 1) were also found during follow-up. CONCLUSION: Neurological symptoms were found to be prevalent among individuals with COVID-19 disease and should not be under-estimated during the current pandemic outbreak.

The effects of augmenting clozapine with oxytocin in schizophrenia: An initial case series.

BACKGROUND: Debilitating symptoms of schizophrenia often persist after sustained treatment with atypical antipsychotics. To date, clozapine has been the most effective of the atypical antipsychotics; however, negative symptoms may persist, indicating a critical need to develop augmenting treatment approaches. METHODS: A retrospective chart review evaluated outcomes for 5 young adult inpatients with treatment-resistant schizophrenia who were prescribed off-label oxytocin (OT; 10 IU/sublingual, 1 time per day, to 20 IU/sublingual, 3 times per day) after their therapeutic response to clozapine plateaued (dose range: 200 to 600 mg). The augmented treatment was well tolerated and continued for at least 1 year after discharge from the hospital, with continued outpatient follow-up by the treating psychiatrist. Evaluation included the Positive and Negative Syndrome Scale and clinical review based on both self and parent/guardian reports. RESULTS: The augmentation of clozapine with sublingual OT in young adults with treatment-resistant schizophrenia appeared to reduce negative symptoms, maintain lowered positive symptoms, and increase occupational and social functioning (eg, return to work or school), as noted by family members. CONCLUSIONS: Future controlled, prospective studies should investigate the possibility that OT can significantly reduce negative symptoms of chronic psychotic illnesses that are inadequately responsive to clozapine or other antipsychotic medications alone.

Impact of depressive symptoms on self-perceived severity of autonomic dysfunction in multiple system atrophy: relevance for patient-reported outcomes in clinical trials.

PURPOSE: To assess the relationship between depressive symptoms and self-perceived severity of autonomic dysfunction in patients with multiple system atrophy (MSA). METHODS: Cross-sectional evaluation of patients with MSA who underwent autonomic testing, Unified MSA Rating Scale (UMSARS)-1 and -2, rating of the presence and severity of depressive symptoms (Zung scale), quality of life (SF-36), body vigilance, anxiety (Spielberger's anxiety scale), severity of autonomic dysfunction with the Composite Autonomic Symptoms Score (COMPASS-31), and severity of orthostatic hypotension (OH) symptoms with the Orthostatic Hypotension Questionnaire (OHQ). RESULTS: Fifty-eight patients (32 women) with probable MSA (aged 61.8 ± 8.6 years; disease duration 4.3 ± 2.1 years) were studied. Forty patients (69%) had symptoms of depression in the Zung scale. Age, disease duration, and motor disability were similar in those with and without symptoms of depression. Despite a similar orthostatic blood pressure fall, the severity of orthostatic symptoms was higher in patients with symptoms of depression (p = 0.004). Depression scores were associated with higher burden of autonomic symptoms (R = 0.401, p = 0.02), specifically with the COMPASS-31 items related to orthostatic intolerance (R = 0.337, p = 0.045), and with the OHQ (R = 0.529; p < 0.001). A multivariable regression model including age, sex, UMSARS, and drop in systolic blood pressure upon head-up tilt as covariates showed that the burden of depressive symptoms was independently associated with the OHQ score: for every 1-unit increase in the Zung depression score, there was a 1.181-point increase in the total OHQ score. CONCLUSIONS: In patients with MSA, depressive symptoms worsen the perceived severity of autonomic symptoms in general and orthostatic hypotension in particular. Our findings have implications for clinical trial design.

Pharmacogenomic Testing in Psychiatry: Ready for Primetime?

Pharmacogenomic testing in clinical psychiatry has grown at an accelerated pace in the last few years and is poised to grow even further. Despite robust evidence lacking regarding efficacy in clinical use, there continues to be growing interest to use it to make treatment decisions. We intend this article to be a primer for a clinician wishing to understand the biological bases, evidence for benefits, and pitfalls in clinical decision-making. Using clinical vignettes, we elucidate these headings in addition to providing a perspective on current relevance, what can be communicated to patients, and future research directions. Overall, the evidence for pharmacogenomic testing in psychiatry demonstrates strong analytical validity, modest clinical validity, and virtually no evidence to support clinical use. There is definitely a need for more double-blinded randomized controlled trials to assess the use of pharmacogenomic testing in clinical decision-making and care, and until this is done, they could perhaps have an adjunct role in clinical decision-making but minimal use in leading the initial treatment plan.

Retrospective Chart Review of Voluntary Admissions to an Inpatient Psychiatric Hospital in New York City: A Demographic Breakdown.

The current paper evaluates psychiatric needs of voluntary admissions in a large urban psychiatric hospital through a retrospective chart review, as this research is limited within the United States. A total of 581 voluntary adult psychiatric admission charts were reviewed. Continuous variables were evaluated using an ANOVA while associations between variables were examined by an unadjusted Pearson correlation coefficient a stepwise linear regression analysis. Men were significantly more likely to have a past admission for psychiatric services (p = .016), suicidal ideation (p < .001) and test positive for substances (p < .001) than women, and were more likely to be unemployed, homeless and without insurance. Women were more likely to have a past suicide attempt and a depressive disorder. A significant relationship between gender and rationale for seeking voluntary admission (p < .001) was found. This study offers understanding of male and female voluntary admissions, and a foundation for improving treatment interventions to reduce recurrent readmissions.

Patient Requests for Discharge from Voluntary Psychiatric Hospitalization: a Chart Review.

The purpose of this study was to examine the rate of 72-hour letters (written requests for discharge, with 72 hours indicating the time the hospital has to discharge or seek retention) placed by voluntary psychiatric inpatients at a New York City hospital and determine whether there are factors contributing to the rates of discharge requests. Charts from all voluntary psychiatric hospitalizations during the calendar year 2007 were retrospectively reviewed. Included were all single voluntary admissions by adults (age 18 years and older) to the hospital. A confirmatory factor analysis (CFA) was conducted with the following factors: urine toxicology, cigarette use on admission, suicidal ideation upon presentation, employment, past inpatient psychiatric admission, and admission day. A linear regression was used to evaluate the relationship between discharge requests and these factors. Of the total sample (N = 581), 119 (20.5%) patients submitted 72-hour letters. The stepwise linear regression analysis confirmed a positive relationship between letter placement and admission day (M = 3.5, SD = 1.7), unemployment (M = 4.7, SD = 2.1), suicidal ideation (M = .5, SD = .5), positive urine toxicology (M = .47, SD = .5), previous psychiatric hospitalization (M = .7, SD = .5) and cigarette usage (M = .5, SD.5) R2 = .043, (6, 461) = 3.42, p = .003). These specific variables accounted for 55.6% of likelihood of a patient submitting a 72-hour letter. Several factors, related to substance and tobacco use, employment, and recurrent use of inpatient services, likely contribute to requests for early discharge. Addressing these factors may help improve inpatient care, reduce costs and improve patient outcomes in the long term.

Opinions Regarding Benzodiazepine Teaching and Prescribing Among Trainees in Psychiatry.

OBJECTIVES: Benzodiazepines are widely prescribed for a variety of symptoms and illnesses. There has been limited investigation on the training psychiatry residents receive regarding benzodiazepine prescribing. This study surveyed US psychiatric trainees about their didactic and clinical experience with benzodiazepines, investigating how experience with benzodiazepines may shape trainees' opinions and likelihood to prescribe. METHODS: The 14-question online survey was distributed to residents and fellows at US training programs through an invitation from their training directors. RESULTS: Of 466 programs contacted, with an estimated 1345 trainees, a total of 97 programs (20.8%) and 424 trainees (31.5%) responded. The analyses focused only on the 342 general psychiatry trainees who responded. Most trainees reported having formal didactics on benzodiazepines, and earlier training was correlated with higher trainee quality of instruction assessments (p < 0.01). Most trainees rated their instructors as Above or Well Above Average. Trainees cited the observation and opinion of supervisors as the two most important factors affecting likelihood of future benzodiazepine prescribing. Trainees commonly reported pressure from patients to prescribe benzodiazepines but were split on perceived pressure from supervisors about prescribing and whether a bias exists against prescribing at their program or in general. CONCLUSION: The survey indicated that psychiatry trainees generally feel adequately trained through didactic and clinical experience with benzodiazepines. Trainees perceived pressure by patients to prescribe benzodiazepines, but generally felt comfortable in managing benzodiazepine usage. Psychiatry attendings' opinions on benzodiazepines most impacted trainees. Influences on trainees' prescribing patterns are important variables that can impact future benzodiazepine prescribing.

Neurologic, psychiatric, and other medical manifestations of nitrous oxide abuse: A systematic review of the case literature.

BACKGROUND/OBJECTIVES: Nitrous oxide (N2 O) is known to have abuse potential, although debate regarding the toxic effects of such abuse continues. Our objective was to review the case literature and present the neurologic, psychiatric and medical consequences of N2 O abuse. METHODS: A systematic literature review was completed for case reports using keywords "nitrous oxide" with "abuse/abusing" or "misuse/misusing" or "overuse/overusing" or "addiction." Non-English-language cases and cases not involving direct toxic effects of N2 O were excluded as were commentaries or personal essays. Clinical presentation, frequency of N2 O abuse, laboratory studies, imaging, ancillary tests, treatments and outcomes were collected from case reports. RESULTS: Our review returned 335 Pubmed, 204 Web of Science, 73 PsycINFO, 6 CINAHL, 55 EMBASE and 0 Grey Literature results, and after exclusion and removal of duplicates, 91 individual cases across 77 publications were included. There were also 11 publications reporting 29 cases of death related to N2 O abuse. The majority of cases (N = 72) reported neurologic sequelae including myeloneuropathy and subacute combined degeneration, commonly (N = 39) with neuroimaging changes. Psychiatric (N = 11) effects included psychosis while other medical effects (N = 8) included pneumomediastinum and frostbite. Across all cases N2 O abuse was correlated with low or low-normal Vitamin B12 (cyanocobalamin) levels (N = 52) and occasionally elevated homocysteine and methylmalonic acid. CONCLUSIONS/SCIENTIFIC SIGNIFICANCE: N2 O abuse represents a significant problem because of the difficulty involved with identification and the toxicity related to chronic abuse including possible death. Health professionals should be aware of the toxic effects of N2 O and be able to identify potential N2 O abuse. (Am J Addict 2016;25:358-369).

Ophthalmologic screening in 25 consecutive geriatric psychiatric inpatient admissions.

In the aging process, people are at increasing risk of visual abnormalities such as cataracts, glaucoma, age-related macular degeneration, and other retinal defects. This holds true for geriatric psychiatric patients as well. These ophthalmic problems may increase risk of falls or increase the comorbidity from dementing processes and depression. Geriatric patients presenting for psychiatric treatment may also be misdiagnosed or under-diagnosed as a result of these visual problems. This quality assurance review of 25 consecutive geriatric psychiatric inpatients demonstrated discrepancies between chart documentation and actual ophthalmologic pathology present in the patients. Doing a simple but complete ophthalmologic screening as part of the general physical examination on admission to an inpatient psychiatric unit can identify those patients who will need more in depth examination of their eyes and promote more accurate differential diagnoses for the patients.

Transient febrile reaction after electroconvulsive therapy (ECT) in a young adult with intellectual disability and bipolar disorder.

We report the case of a 27-year-old man with mild-moderate intellectual disability (ID) and bipolar disorder treated with electroconvulsive therapy (ECT). He was psychiatrically hospitalized for agitation, aggression, and manic symptoms including insomnia, rapid and pressured speech, and hyperactivity. After multiple medication trials, ECT was recommended. The treatment was delayed owing to the need to obtain evaluation for incapacity and then substituted consent from the patient's mother. He received 2 ECT treatments with marked improvement but complicated by transient fevers, which resolved without treatment. Fever workup was unremarkable. The patient became calm and cooperative and was discharged home. He was readmitted 3 weeks later, again in an agitated manic state. He received 5 additional ECT treatments, but this time with no post-ECT fevers. Once again, his manic symptoms resolved, and he was safely discharged. Whereas patients with ID pose special challenges, our case is in keeping with the previous literature, which supports the use of ECT in patients with ID and comorbid psychiatric disorders.

Electroconvulsive therapy (ECT) for catatonia in a patient with schizophrenia and synthetic cannabinoid abuse: a case report.

We present the case of a young man with a long-standing history of schizophrenia who presented with severe and life-threatening catatonia in the setting of synthetic cannabis use who was successfully treated with electroconvulsive therapy. To our knowledge, this is the first reported case of severe and persistent catatonia in the setting of synthetic cannabis use and the first documented successful treatment.

Mental health approaches to child victims of acts of terrorism.

It has long been recognized that human beings exposed to severe stress may develop psychological symptoms. With recent terrorist acts around the world including the New York City World Trade Center September 11, 2001 atrocity, there has been a growing interest in the specific impact of terrorist acts on the victims and witnesses. One area that has received less study is the specific impact on children. This paper reviews some of the general effects of traumatic stress on children and the history of the research in this area including a specific discussion of post-traumatic stress disorder in children. This is followed by a review of how children might react to the trauma of a terrorist attack differentiating between three different subgroups of children (preschool age children, school-age children, and adolescents). Then there is a review of what a comprehensive evaluation of childhood victims of terrorism should entail. Finally, treatment modalities that have been shown to be effective are reviewed.

Commentary: Mania in Medically Ill Patients.

Patients may present with manic symptoms in medical settings such as emergency rooms and on inpatient medical floors, leading to psychiatric consultation to try to determine the etiology of the symptoms. It is crucial to clarify whether the mania is secondary to a medical illness or whether the patient's symptoms are from a primary bipolar disorder. In this issue, we publish 2 case reports of patients presenting with manic symptoms in medical settings. The first case involves polymicrogyria in the frontal lobe of the brain as a cause of secondary mania. The second case involves a patient who was previously diagnosed with bipolar disorder and subsequently developed symptoms of Behçet's disease. In this case, it appears likely that the bipolar disorder was primary, and that the Behçet disease and the bipolar disorder may have exacerbated each other. Given the complexities involved in assessing and treating patients, especially in acute or emergency settings, it is important for primary medical and psychiatric providers to collaborate and communicate well in assuring that they obtain a thorough history of their patients' symptoms and that patients receive a comprehensive medical evaluation before psychiatric treatment is started.

Disparities in program enrollment and employment outcomes for veterans with psychiatric and co-occurring substance use disorders referred or enrolled for VHA vocational rehabilitation.

Introduction: The purpose of the study was to investigate factors that influence vocational rehabilitation program enrollment and employment at discharge of veterans with psychiatric and co-occurring alcohol and other substance use disorders enrolled at a veteran health administration (VHA) medical center. Methods: A sample of 2,550 veteran patients referred for VHA vocational rehabilitation between 2016 and 2021 were examined for the current study. The current study was classified as quality improvement/assurance, thus resulting in exempt research by the U.S. Department of Veteran Affairs Institutional Review Board. Results: Veterans with active alcohol use disorders (AUDs) and co-occurring depression, anxiety, post-traumatic stress disorder, or bipolar disorders were less likely to be enrolled for vocational rehabilitation program services compared to those without these co-occurring diagnoses. Veterans with AUD (active & in-remission status combined into one category) and a diagnosis of anxiety were less likely to be employed at discharge compared to veterans with AUDs and no anxiety diagnosis (anxiety diagnosis - 3.5% vs. no anxiety diagnosis - 5.8%). Discussion: VHA vocational rehabilitation can be an effective intervention to assist veterans in reintegrating back into the community. Yet, there appears to be some disparities in the program enrollment and employment at discharge, depending on the nature of the psychiatric diagnosis. Investigating the factors contributing (mediating or moderating) to these discrepancies are needed. Although it appears access is not the issue in being referred for vocational rehabilitation services, other factors are likely contributing to program entry.

Psychedelics, With a Focus on Psilocybin: Issues for the Clinician.

There has been a burgeoning interest in psychedelics among the public, state legislatures, psychiatrists and other clinical providers, and within the research community. Increasing numbers of studies evaluating psychedelics for depression, anxiety, posttraumatic stress disorder, and substance use disorders have been conducted or are underway. While discussing psychedelics in general, the focus of this paper is on psilocybin and its mechanism, how it exerts a psychedelic effect, dosing, and a review of the treatment studies of psilocybin, which were primarily for treatment-resistant depression and cancer-related anxiety. Future directions and potential limitations of studying and regulating psilocybin and other psychedelics are also discussed.

Proinflammatory and "resiliency" proteins in the CSF of patients with major depression.

BACKGROUND: A number of studies have shown that elevated levels of inflammatory cytokines may promote depression and suicidal ideation and that neuroprotective peptides may decrease the response to stress and depression. In this study, cerebrospinal fluid (CSF) levels of three inflammatory cytokines (IL-1, IL-6, and tumor necrosis factor α (TNFα)) and two putative "resiliency" neuropeptides (brain-derived neurotrophic factor (BDNF) and neuropeptide Y (NPY)) were compared between patients with depression and healthy controls. METHODS: Eighteen patients with major depression and 25 healthy controls underwent a lumbar puncture; CSF samples were withdrawn and assayed for IL-1, IL-6, TNFα, BDNF, and NPY levels. Patients with depression were then entered into an 8-week treatment protocol and had repeated lumbar puncture procedures post-treatment. RESULTS: Contrary to prediction, we found that at baseline depressed patients had higher CSF NPY concentration compared to the normal comparison group. Within the depressed patients, we found several statistically significant correlations between elevated CSF cytokine levels and clinical severity. CONCLUSION: Despite the small sample size, given the challenges in obtaining CSF from patients with depression these data are of interest in confirming some aspects of the inflammatory hypothesis of depression.