A Systematic Review of Clozapine Concentration-Dose Ratio from Therapeutic Drug Monitoring Studies in Children and Adolescents Treated with Clozapine for Mental Disorders.

BACKGROUND: Therapeutic drug monitoring of clozapine in children and adolescents has received insufficient attention. Calculation of concentration-to-dose (C/D) ratios from trough steady-state concentrations estimate drug clearance. METHODS: A systematic electronic literature search was conducted in 3 article databases from inception until January 10, 2023, and articles reporting clozapine concentrations in children and adolescents were retrieved. The pharmacokinetic quality of the studies was assessed, and clozapine C/D ratios were calculated using the sample mean clozapine dose and concentration. RESULTS: Of the 37 articles of potential interest, only 7 reported clozapine trough and steady-state concentrations. After excluding case reports and a study confounded by fluvoxamine, 4 studies on psychosis from Europe and the United States were included. The clozapine C/D ratios were similar to published adult values and ranged from 0.82 to 1.24 with a weighted mean of 1.08 ng/mL per mg/d. The weighted means were 334 mg/d for the dose and 380 ng/mL for the concentration. The stratified analysis of the weighted mean clozapine C/D ratios from 2 studies showed lower values in 52 male (1.05 ng/mL per mg/d) than in 46 female (1.46 ng/mL per mg/d) children and adolescents, with values similar to those reported for European adult nonsmokers. Two female adolescents had high clozapine C/D ratios (2.54 ng/mL per mg/d), an Asian American patient with borderline obesity and a patient with intellectual disability with low dosage (mean = 102 mg/d) and concentration (mean = 55 ng/mL). CONCLUSIONS: Reports on clozapine therapeutic drug monitoring in children and adolescents are limited in number and quality. Future studies should focus on basic pharmacokinetic issues, such as stratification by sex, smoking, and relevant comedications with inductive or inhibitory properties.

THE HEALING POWER OF TALK THERAPY.

The Word (λόγος or logos in Greek, verbum in Latin) is an exclusive attribute of a rational animal such as the human, who shares non-verbal language with other animal species.

Oxidative stress parameters and antioxidants in adults with unipolar or bipolar depression versus healthy controls: Systematic review and meta-analysis.

BACKGROUND: To study differences in oxidative stress markers and antioxidants among patients with bipolar depression (BPD) and unipolar depression (UPD). METHODS: Data sources. Electronic MEDLINE/PubMed/Cochrane Library/Scopus/TripDatabase database search until 30/06/2021. STUDY SELECTION: Included were articles comparing antioxidant or oxidative stress markers between adults with BPD or UPD and healthy controls (HCs). DATA EXTRACTION: Two authors extracted data independently. Random effects meta-analysis, calculating standardized mean differences for results from ≥3 studies. RESULTS: Oxidative stress markers reported in 40 studies -1 published repeatedly- (UPD, studies = 30 n = 3072; their HCs, n = 2856; BPD, studies = 11 n = 393; their HCs, n = 540; with 1 study reporting on both UPD and BPD) included thiobarbituric acid reactive substances (TBARS), antioxidant uric acid and antioxidant-enhancing enzymes superoxide dismutase (SOD), catalase (CAT) and glutathione-peroxidase (GPX). Compared with HCs, UPD and BPD were associated with significantly higher levels of TBARS, without differences between UPD and BPD (P = 0.11). Compared with HCs, UPD and BPD did not differ regarding the activity of the CAT (P = 0.28), SOD (P = 0.87) and GPX (P = 0.25) enzymes. However, uric acid levels were significantly higher vs HCs in BPD than in UPD among adult patients (P = 0.004). Results were heterogenous, which, for some parameters, decreased after stratification by the blood source (serum, plasma red blood cells, whole blood). LIMITATIONS: The main limitations are the small number of studies/participants in the BPD subgroup, and heterogeneity of the results. SUMMATIONS: Both BPD and UPD may be associated with an impaired oxidative stress balance, with significantly higher uric acid levels vs. HCs in UPD than in BPD.

Oxidative stress parameters and antioxidants in patients with bipolar disorder: Results from a meta-analysis comparing patients, including stratification by polarity and euthymic status, with healthy controls.

OBJECTIVE: To investigate oxidative stress markers and antioxidants in bipolar disorder (BD). METHODS: Electronic MEDLINE/PubMed/Cochrane-Library/Scopus/TripDatabase search until 06/30/2019 for studies comparing antioxidant or oxidative stress markers between BD and healthy controls (HCs). Standardized mean differences (SMD) and 95% confidence intervals (CIs) were calculated for ≥3 studies. RESULTS: Forty-four studies (n = 3,767: BD = 1,979; HCs = 1,788) reported on oxidative stress markers malondialdehyde (MDA), thiobarbituric acid reactive substances (TBARS), and total nitrites; antioxidants glutathione (GSH), uric acid, and zinc; or antioxidantenhancing enzymes superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX), and GSH-transferase (GST). Compared with HCs, BD was associated with higher GST (P = .01), CAT (P = .02), nitrites (P < .0001), TBARS (P < .0001), MDA (P = .01), uric acid (P < .0001), and lower GSH (P = .006), without differences in SOD, GPX, and zinc. Compared to HCs, levels were higher in BD-mania for TBARS (P < .0001) and uric acid (P < .0001); in BD-depression for TBARS (P = .02); and BD-euthymia for uric acid (P = .03). Uric acid levels were higher in BD-mania vs BD-depression (P = .002), but not vs BD euthymia. TBARS did not differ between BD-mania and BD-depression. Medication-free BD-mania patients had higher SOD (P = .02) and lower GPX (P < .0001) than HCs. After treatment, BD did not differ from HCs regarding SOD and GPX. CONCLUSIONS: Beyond a single biomarker of oxidative stress, the combination of several parameters appears to be more informative for BD in general and taking into account illness polarity. BD is associated with an imbalance in oxidative stress with some phase-specificity for uric acid and TBARS and possible treatment benefits for SOD and GPX. Future studies should take into account confounding factors that can modify oxidative stress status and simultaneously measure oxidative stress markers and antioxidants including different blood sources.

Features Associated With Depressive Predominant Polarity and Early Illness Onset in Patients With Bipolar Disorder.

Objective: The aim of this study is to determine the prevalence of three possible diagnostic specifiers, namely predominant polarity (PP) throughout illness, polarity of the first episode and early age at onset, in a sample of bipolar disorder (BD) patients and their association with important socio-demographic, clinical and course-of-illness variables. Methods: A retrospective and naturalistic study on 108 BD outpatients, who were classified according to the PP, polarity of the first episode and early age at onset (≤ 20 years) [vs. late (>20 years)] and were characterized by their demographics, clinical data, functionality and social support, among others features. After bivariate analyses, those variables showing certain association (P value < 0.25) with the three dependent variables were entered in logistic regression backward selection procedures to identify the variables independently associated with the PP, polarity of the first episode and early age at onset. Results: The sample consisted of 75 women ad 33 men, 74% with type I BD and 26% with type II. Around 70% had depressive PP, onset with a depressive episode and onset after age 20. Depressive PP was independently associated with depressive onset, higher score on the CGI severity scale and work disability. Onset with depressive episode was associated with type II BD, longer diagnostic delay and higher score on family disability. Early age at onset (≤ 20 years) was associate with younger age, longer diagnostic delay, presence of ever psychotic symptoms, current use of antipsychotic drugs and higher social support score. Conclusions: The results of this study show that BD patients with depressive PP, onset with depression and early age at onset may represent greater severity, because they are frequently associated with variables that worsen the prognosis. Our findings match up with the conclusions of two systematic reviews and we also include a disability factor (at family and work) that has not been previously reported. This work contributes to the use of polarity and age at onset in BD patients, as it can become a useful instrument in the prognostic and therapeutic applications.

Illness Insight and Medication Adherence Among Patients With Bipolar Disorder.

The aim of this study was to investigate the factors associated with illness insight and medication adherence in bipolar disorder (BD). This is a cross-sectional study (with a retrospective evaluation of longitudinal variables) and a secondary analysis of a BD database. The insight of 108 outpatients (age, 48.2 ± 14.1 years, 69% women, 33% euthymic) was measured with three items of the Association of Methodology and Documentation in Psychiatry scale. Their adherence was assessed through patients' and caregivers' reports, plus serum levels. We performed multivariate logistic regression analyses. Full insight was independently and directly associated with adherence, a social support score, and depressive symptoms and inversely associated with intensity of manic symptoms, problems ever with alcohol, and age at onset of the first symptoms. Medication adherence was independently and directly associated with insight, being married, and having had a psychiatric hospitalization and inversely with having suffered a high number of depressive episodes, intensity of manic symptoms, and heavy tobacco smoking.

Quality of life, anxiety and depressive symptoms in patients with psoriasis: A case-control study.

OBJECTIVE: To compare quality of life (QoL), anxiety and depressive symptoms, alcohol consumption and other correlates between patients with psoriasis and controls; and to identify features of psoriasis associated with lower levels of QoL. METHOD: Case-control study including 70 subjects with moderate-severe psoriasis and 140 controls without psoriasis. All participants answered the Short Form Health Survey (SF-36), with physical and mental component scores of quality of life, and the Hospital Anxiety and Depression Scale (HADS). Among subjects with psoriasis, the Psoriasis Area and Severity Index (PASI) and the Dermatology Life Quality Index (DLQI) were used, respectively, to measure the severity of psoriasis and the impact of psoriasis on the specific quality of life. RESULTS: Compared to controls, patients with psoriasis showed higher HADS depression score and alcohol consumption, and lower QoL. Among subjects with psoriasis, multivariate analysis showed: 1) poorer physical QoL was associated with older age, articular lesions and anxious symptoms, whereas poorer mental QoL was associated with younger age, female sex, genital lesions and depressive symptoms; 2) the higher the severity of psoriasis, the lower the level of QoL and the higher the levels of anxious or depressive symptoms; and 3) female sex and articular or genital location of lesions are linked with higher HADS scores. CONCLUSION: Higher scores in anxiety and depression and lower QoL is common in psoriasis, especially among women and those with genital or articular lesions. Dermatologists should give special attention to this subgroup of persons with psoriasis in order to prevent future psychopathology.

Disordered eating behaviors among Christian and Muslim adolescents in Ceuta, a multicultural town.

Studies on disordered eating behaviors (DEB) in multicultural populations with multiple religious/cultural affiliations are needed in order to clarify the relationship between cultural background and DEB. Therefore, we compared the presence of DEB among Christian and Muslim adolescents who share their school environment, controlling for the effect of body mass index, demographic variables and lifestyle habits. A sample of 493 girls and boys (339 Christian, 138 Muslim) whose mean (±SD) age was 14.8 (±1.7) years completed self-reporting questionnaires and underwent measurements of anthropometric data. Religious/cultural affiliation was defined by self-identification. The dependent variable, DEB was assessed by means of the Eating Disorders Inventory (EDI-2). Muslim girls and boys score higher than Christians on EDI-2 total scores, especially on the perfectionism subscale. Bivariate and multivariate analyses were used to determine the characteristics associated with DEB, which were detected in 24% of participants (19% of Christians and in 35% of Muslims). Among girls, DEB were directly associated with overweight or obesity, the presence of frequent quarrels with parents, academic failure and spending more than 3 h a day watching screen images. Among boys, DEB were directly associated with overweight or obesity and Muslim background; and inversely associated with age and socioeconomic status.

Temperament traits and remission of depression: A naturalistic six-month longitudinal study.

BACKGROUND: The aim of this naturalistic longitudinal study was to add evidence regarding the potential of Cloninger's temperament traits (novelty seeking, harm avoidance, reward dependence and persistence) for predicting the effect of pharmacological treatment on the rates of therapeutic response and remission. METHODS: The study was based on 200 outpatients with unipolar depressive disorders of different severity and course of illness, and extended up to 6 months of follow-up. Patients were assessed in their temperament with the Tridimensional Personality Questionnaire (TPQ) and their condition was classified (in course and severity) according to the International Classification of Diseases, Tenth revision (ICD-10) diagnostic criteria for research. Patients were blindly rated (concerning other predicting variables) on the improved Clinical Global Impression-Severity scale for depression (iCGI-S) at baseline, 6 weeks, 3 months and 6 months. Outcome measures at the last observation carried forward were therapeutic response (reduction of ≥50% in the last iCGI-S) and remission (last iCGI-S = 0), which were available for 187 patients. RESULTS: Remission was independently and directly associated with length of follow-up, and inversely with the baseline iCGI-S score and harm avoidance (patients in the high tertile had a 2.7 likelihood of non-remission in comparison with those in the low tertile); persistence was found to have a complex, V-shape relationship with remission. Within a sub-sample of more severe cases (n = 118), having higher harm avoidance scores, a more favorable outcome was associated with higher reward dependence and the non-smoking condition. LIMITATIONS: With a naturalistic, non-experimental design, the sample may not be representative of the general population. CONCLUSIONS: Temperament traits may help predict outcome in patients treated for depression.

Factores asociados a malestar psicológico o trastornos mentales comunes en poblaciones migrantes a lo largo del mundo / Factors associated with psychological distress or common mental disorders in migrant populations across the world

Se revisan sistemáticamente los factores asociados a la presencia de malestar psicológico o trastornos mentales comunes en poblaciones migrantes. Se revisaron los artículos publicados entre enero de 2000 y diciembre de 2014, de los que se seleccionaron 85 que aplicaban análisis estadísticos multivariantes. Los trastornos mentales comunes se asociaban significativamente a características sociodemográficas y psicológicas, lo mismo que se observa en grandes estudios epidemiológicos de poblaciones generales. La probabilidad de trastornos mentales comunes aumentó significativamente entre grupos de migrantes, además de por la región de origen, por los siguientes factores: sucesos traumáticos previos; migración forzosa, escasamente planificada o ilegal; bajo nivel de aculturación, vivir solo o separado de la familia en el nuevo país, falta de apoyo social, discriminación percibida y tiempo transcurrido en el nuevo país. Para diseñar estrategias preventivas se ha de tener en cuenta los factores asociados al riesgo de morbilidad psiquiátrica en poblaciones migrantes (AU)

We systematically review factors associated with the presence of psychological distress or common mental disorders in migrant populations. Articles published between January 2000 and December 2014 were reviewed and 85 applying multivariate statistical analysis were selected. Common mental disorders were significantly associated with socio-demographic and psychological characteristics, as observed in large epidemiological studies on general populations. The probability of common mental disorders occurrence differs significantly among migrant groups according to their region of origin. Moreover, traumatic events prior to migration, forced, unplanned, poorly planned or illegal migration, low level of acculturation, living alone or separated from family in the host country, lack of social support, perceived discrimination, and the length of migrants’ residence in the host country all increase the likelihood of CMD. In contrast, language proficiency, family reunification, and perceived social support reduce such probability. Factors related with the risk of psychiatric morbidity among migrants should be taken into account to design preventive strategies (AU)

Temporal sequencing of nicotine dependence and major depressive disorder: A U.S. national study.

Major Depressive Disorder (MDD) and Nicotine dependence (ND) often co-occur. However, little attention has been given to the temporal order between the two disorders. We compared the sociodemographic and clinical characteristics of individuals whose onset of ND preceded (ND-prior) or followed the onset of MDD (MDD-prior). Binary logistic regression models were computed to compare ND-prior (n=546) and MDD-prior (n=801) individuals from the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC, n=43,093). We found that MDD-prior were more likely to have a history of suicide attempts and a family history of both depression and antisocial behavior, to have had psychiatric hospitalization, and to have an earlier age of onset of the first depressive episode; but a later age of onset for both daily smoking and ND. On average, MDD-prior individuals showed a significantly longer transition time from daily smoking to ND (15.6±0.6 vs. 6.9±0.4 years, P<0.001). In contrast, ND-prior subjects had a significantly greater proportion of withdrawal symptoms, and of lifetime alcohol use or alcohol use disorder. We conclude that the phenomenology and course of ND and MDD vary significantly, depending on which disorder had earlier onset.

Factors associated with psychological distress or common mental disorders in migrant populations across the world. / Factores asociados a malestar psicológico o trastornos mentales comunes en poblaciones migrantes a lo largo del mundo.

We systematically review factors associated with the presence of psychological distress or common mental disorders in migrant populations. Articles published between January 2000 and December 2014 were reviewed and 85 applying multivariate statistical analysis were selected. Common mental disorders were significantly associated with socio-demographic and psychological characteristics, as observed in large epidemiological studies on general populations. The probability of common mental disorders occurrence differs significantly among migrant groups according to their region of origin. Moreover, traumatic events prior to migration, forced, unplanned, poorly planned or illegal migration, low level of acculturation, living alone or separated from family in the host country, lack of social support, perceived discrimination, and the length of migrants' residence in the host country all increase the likelihood of CMD. In contrast, language proficiency, family reunification, and perceived social support reduce such probability. Factors related with the risk of psychiatric morbidity among migrants should be taken into account to design preventive strategies.

Oxidative stress and antioxidant parameters in patients with major depressive disorder compared to healthy controls before and after antidepressant treatment: results from a meta-analysis.

OBJECTIVE: To investigate the role of oxidative stress and antioxidants in depression. DATA SOURCES: We searched the literature without language restrictions through MEDLINE/PubMed, Cochrane Library, Fisterra, and Galenicom from database inception until December 31, 2013, supplemented by a hand search of relevant articles. Search terms included (1) oxidative stress, antioxidant*, nitrosative stress, nitrative stress, nitro-oxidative stress, free radical*, and names of individual oxidative stress markers/antioxidants and (2) depression and related disorders and antidepressant. STUDY SELECTION: Included were studies in patients with depression comparing antioxidant or oxidative stress markers with those in healthy controls before and after antidepressant treatment. DATA EXTRACTION: Two authors independently extracted the data for antioxidant or oxidative stress markers. Standardized mean differences (SMDs) ± 95% confidence intervals (CIs) for results from ≥ 3 studies were calculated. DATA SYNTHESIS: Altogether, 29 studies (N = 3,961; patients with depression = 2,477, healthy controls = 1,484) reported on the oxidative stress marker malondialdehyde (MDA) and total nitrites, the antioxidants uric acid and zinc, or the antioxidant-enhancing enzymes superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPX). When patients with depression were compared with healthy controls, depression was associated with higher oxidative stress MDA levels (8 studies; n = 916; SMD = 1.34; 95% CI, 0.57 to 2.11; P < .001), lower antioxidant uric acid (4 studies; n = 512; SMD = -0.64; 95% CI, -1.22 to -0.06; P = .030) and zinc levels (13 studies; n = 2,002; SMD = -0.66; 95% CI, -0.98 to -0.34; P < .0001), and higher antioxidant-enhancing enzyme SOD levels (11 studies; n = 902; SMD = 0.62; 95% CI, 0.07 to 1.17; P = .028), while differences in total nitrites and CAT and GPX were nonsignificant. Antidepressant treatment, which significantly reduced Hamilton Depression Rating Scale scores (24.6 ± 0.7 to 16.2 ± 1.6; SMD = 2.65; 95% CI, 1.13 to 4.15; P = .00065), reduced MDA (4 studies; n = 194; SMD = -1.45; 95% CI, -2.43 to -0.47; P = .004) and increased uric acid (3 studies; n = 212; SMD = 0.76; 95% CI, 0.03 to 1.49; P = .040) and zinc levels (3 studies; n = 65; SMD = 1.22; 95% CI, 0.40 to 2.04, P = .004), without differences in MDA (P = .60), uric acid (P = .10), and zinc (P = .163) levels compared to healthy controls. CONCLUSIONS: Results suggest that oxidative stress plays a role in depression and that antidepressant activity may be mediated via improving oxidative stress/antioxidant function.

Childhood trauma as a risk factor for psychosis: A sib-pair study.

BACKGROUND: Childhood trauma, cannabis use and certain personality traits have been related to the development of psychosis. This study uses a sib-pair design to examine the association between childhood trauma and psychosis controlling for cannabis use and neuroticism. METHODS: We evaluated 60 patient-sibling pairs, conformed by patients with functional psychosis in the first five years of their illness matched with a non-psychotic sibling. In univariate analyses, patients and siblings were compared with McNemar tests and paired-sample t tests. A conditional logistic regression model of the risk of developing psychosis was built. The dependent variable of this model was the patient-sibling status (patient = 1, sibling = 0). RESULTS: After controlling for cannabis use and neuroticism, the odds of suffering psychosis for subjects who experienced a childhood trauma were 7.3 times higher than the odds for subjects who did not experience a childhood trauma [95% CI, (1.06-50.01); P = 0.04]. Also, after controlling for experiencing childhood trauma and neuroticism, subjects who were heavy cannabis users had odds of suffering psychosis that were 6.4 times higher than the odds of the remaining subjects [95% CI, (1.2-35.2); P = 0.03]. CONCLUSION: Both childhood trauma and cannabis use were significantly associated with an increased risk of suffering functional psychosis. A neurotic personality also contributed independently to this risk. These findings might help improve the prevention of psychosis and the development of specific treatment strategies on this specific population.

Caffeine consumption in a long-term psychiatric hospital: Tobacco smoking may explain in large part the apparent association between schizophrenia and caffeine use.

This study further explores the association between schizophrenia and caffeine use by combining two prior published Spanish samples (250 schizophrenia outpatients and 290 controls from the general population) with two Spanish long-term inpatient samples from the same hospital (145 with schizophrenia and 64 with other severe mental illnesses). The specific aims were to establish whether or not, after controlling for confounders including tobacco smoking, the association between schizophrenia and caffeine is consistent across schizophrenia samples and across different definitions of caffeine use. The frequency of caffeine use in schizophrenia inpatients was not significantly higher than that in non-schizophrenia inpatients (77%, 111/145 vs. 75%, 48/64) or controls but was significantly higher than in schizophrenia outpatients. The frequency of high caffeine users among caffeine users in schizophrenia inpatients was not significantly higher than in non-schizophrenia inpatients (45%, 50/111 vs. 52%, 25/48) or controls, but was significantly lower than in schizophrenia outpatients. Smoking was significantly associated with caffeine use across all samples and definitions. Between 2 and 3% of schizophrenia inpatients, schizophrenia outpatients and non-schizophrenia inpatients showed caffeinism (>700 mg/day in smokers). Several of these smoking patients with caffeinism were also taking other inducers, particularly omeprazole. The lack of consistent association between schizophrenia and caffeine use is surprising when compared with the very consistent association between tobacco smoking and caffeine use across all of our analyses (use and high use in users) and all our samples. The confounding effects of tobacco smoking may explain in large part the apparent association between schizophrenia and caffeine use.

World region of origin and common mental disorders among migrant women in Spain.

Migration can affect the mental health of migrants. This cross-sectional study has two objectives: (1) to compare the prevalence of common mental disorder (CMD) between migrants (n = 458) living in Granada (Spain) and Spanish-born women (n = 448); (2) within migrants, to analyse the associations of world region of origin, other sociodemographic factors and post-migration features with the presence of CMD. Participants answered a questionnaire, including sociodemographic characteristics, post-migration features and CMD that was measured by Kessler K6-scale. Logistic regression analyses showed that CMD (K6 ≥ 13) was significantly higher among migrants than Spaniards. Compared with Spaniards, the odds of CMD were 3.6 [95 % confidence intervals (CI) 2.1­6.0] and 2.9 (CI 1.6­5.3), respectively, for Latin Americans and for Moroccan and other African women. Among migrants, Latin Americans as opposed to the reference group (migrants from other countries), had higher probability of CMD (OR 2.3, CI 1.1­4.9). This study supports the hypothesis that migration leads to mental distress. Consideration of world region of origin may clarify the differences observed in mental health across different migrant groups.

Phosphate levels as a possible state marker in panic disorder: preliminary study of a feasible laboratory measure for routine clinical practice.

OBJECTIVE: Low serum phosphate level is considered one of the metabolic adaptations to the respiratory alkalosis induced by hyperventilation associated with panic disorder. The aim of this study was to assess phosphatemia as a possible state marker for panic disorder. METHODS: Sixteen panic disorder patients underwent clinical assessment with a semi-structured interview, a set of rating scales and the self-rated State and Trait Anxiety Inventory (STAI), as well as extraction of venous blood samples at baseline and after 12 weeks of pharmacological treatment. Ten healthy volunteers of similar sex, age and educational level filled out the STAI and gave blood samples at baseline and 12 weeks later. RESULTS: The median (25th-75th percentiles) of phosphate levels (mg/dl) was 2.68 (2.22-3.18) among patients and 4.13 (3.74-4.70) among healthy volunteers respectively (P < 0.001). Seven (44%) patients and no healthy volunteers presented low serum phosphate (<2.50 mg/dl) at baseline; this patient abnormality was corrected in all cases after successful treatment. At baseline, the age-adjusted correlation between phosphate levels and state-anxiety was -0.66 (P < 0.001) among all 26 participants and -0.51 (P = 0.05) among the 16 panic disorder patients. CONCLUSIONS: Measurement of phosphate levels could be easily introduced into clinical practice as a possible marker for chronic hyperventilation in panic disorder, although further investigations with larger sample sizes are necessary to characterize panic disorder patients with low versus normal phosphate levels.