Characterisation of the urinary steroid profile of patients with nonfunctioning adrenal incidentalomas: A matched controlled cross-sectional study.

AIM: To identify alterations in steroid metabolism in patients with nonfunctioning adrenal incidentalomas (NFAIs) through the analysis of their urinary steroid profile (USP). METHODS: Cross-sectional study with one study group (NFAIs, cortisol post dexamethasone suppression test [DST] ≤ 1.8 µg/dl [49.7 nmol/L]) and 2 control groups: patients with autonomous cortisol secretion (ACS group, cortisol post-DST > 1.8 µg/dl (49.7 nmol/L) and patients without adrenal tumours (healthy-adrenal group). Twenty-four-hour urine collections for USP measurement (total and free fraction of 51 24 h-urine specimens) were obtained from 73 participants (24 with NFAIs, 24 without AIs, and 25 with ACS). USP was determined by gas chromatography coupled to mass spectrometry. Patients of the three groups were matched according to sex, age (±5 years-old) and body mass index (±5 kg/m2 ). RESULTS: Compared to healthy-adrenal controls, patients with NFAIs had a lower excretion of androgen metabolites (230.5 ± 190.12 vs. 388.7 ± 328.58 µg/24 h, p = .046) and a higher excretion of urinary free cortisol (UFC) (54.3 ± 66.07 vs. 25.4 ± 11.16 µg/24 h, p = .038). UFC was above the reference range in 20.8% of patients in the NFAI, compared to 0% in the healthy-adrenal group (p = .018). Patients with ACS had a higher prevalence of hypertension, dyslipidemia, and diabetes than patients with NFAIs or the control group. A lower excretion of androgen metabolites (218.4 ± 204.24 vs. 231 ± 190 µg/24 h, p = .041) and a nonsignificant higher excretion of glucocorticoid metabolites (2129.6 ± 1195.96 vs. 1550.8 ± 810.03 µg/24 h, p = .180) was found in patients with ACS compared to patients with NFAIs. CONCLUSION: NFAIs seem to secrete a subtle, yet clinically relevant, excess of glucocorticoids. Future studies are needed to confirm our findings; and to identify metabolic alterations associated with an increased cardiometabolic risk.

Causes of hyperprolactinaemia in the primary care setting: How to optimise hyperprolactinaemia management.

BACKGROUND AND PURPOSE: To analyse the causes of hyperprolactinaemia in patients with symptoms compatible with hyperprolactinaemia evaluated in a primary care setting. PATIENTS AND METHODS: A retrospective study of all patients tested for serum prolactin levels between 2019 and 2020 in 20 primary care centres at the Hospital Ramón y Cajal in Madrid. Hyperprolactinaemia is defined as a serum prolactin>19.4ng/ml in men and >26.5ng/ml in women. Aetiology is grouped into physiological (pregnancy, lactation, inadequate venipuncture, macroprolactinaemia), pharmacological, pathological (hypothalamic and/or pituitary diseases, chronic renal failure, primary hypothyroidism), and idiopathic. RESULTS: In 1630 patients tested for serum prolactin, 30.7% (n=501) had hyperprolactinaemia. Of these 501 patients, 89.6% were females. 149 patients were referred to the Endocrinology Department and 164 to the Gynaecology Department. Aetiological diagnosis of hyperprolactinaemia was achieved in 411 out of 501 cases. The most frequent cause of hyperprolactinaemia was pharmacological, in 39.1%. The second more frequent cause was idiopathic (29%) and less common were inadequate venipuncture extraction (13.4%), tumour (8.5%) and macroprolactinaemia (3.9%). Patients with tumoural hyperprolactinaemia presented higher serum prolactin levels (87.0±80.19 vs 49.7±39.62ng/ml, P=0.010). In addition, symptoms, such as galactorrhoea (33.3% vs 16.5%, P=0.018), and headache (25.7% vs 13.3%, P=0.045), were more frequent than in patients of the other aetiological groups. CONCLUSION: Hyperprolactinaemia is common among patients evaluated in a primary care setting with symptoms of hyperprolactinaemia, but more than 50% of cases are due to pharmacological treatments or improper sample extraction. It is necessary to establish referral protocols to specialised medicine to optimise healthcare resources and avoid unnecessary studies.

The Role of Premorbid IQ and Age of Onset as Useful Predictors of Clinical, Functional Outcomes, and Recovery of Individuals with a First Episode of Psychosis.

BACKGROUND: premorbid IQ (pIQ) and age of onset are predictors of clinical severity and long-term functioning after a first episode of psychosis. However, the additive influence of these variables on clinical, functional, and recovery rates outcomes is largely unknown. METHODS: we characterized 255 individuals who have experienced a first episode of psychosis in four a priori defined subgroups based on pIQ (low pIQ < 85; average pIQ ≥ 85) and age of onset (early onset < 18 years; adult onset ≥ 18 years). We conducted clinical and functional assessments at baseline and at two-year follow-up. We calculated symptom remission and recovery rates using the Positive and Negative Symptoms of Schizophrenia Schedule (PANSS) and the Global Assessment Functioning (GAF or Children-GAF). We examined clinical and functional changes with pair-wise comparisons and two-way mixed ANOVA. We built hierarchical lineal and logistic regression models to estimate the predictive value of the independent variables over functioning or recovery rates. RESULTS: early-onset patients had more severe positive symptoms and poorer functioning than adult-onset patients. At two-year follow-up, only early-onset with low pIQ and adult-onset with average pIQ subgroups differed consistently, with the former having more negative symptoms (d = 0.59), poorer functioning (d = 0.82), lower remission (61% vs. 81.1%), and clinical recovery (34.1% vs. 62.2%). CONCLUSIONS: early-onset individuals with low pIQ may present persistent negative symptoms, lower functioning, and less recovery likelihood at two-year follow-up. Intensive cognitive and functional programs for these individuals merit testing to improve long-term recovery rates in this subgroup.

Translation and validation of Baron Cohen’s face test in a general population from Spain.

Facial emotion recognition is considered the foundation of effective social functioning, but it has been found impaired in several clinical populations. How- ever, there are few validated tests to measure the ability. To the best of our knowledge, there is no validated measure in a Spanish population. We translated and validated Baron Cohen’s Face Test in a general Spanish population.

Traducción y validación del test de caras de Baron Cohen en población española / Translation and validation of Baron Cohen’s face test in a general population from Spain

Introducción: El reconocimiento facial de emociones esesencial en el funcionamiento social adecuado. Se han encontrado déficits en muchas poblaciones clínicas. Hay pocostests validados que midan esta habilidad y ninguno en población española. En este trabajo, tradujimos y validamos elTest de Caras de Baron Cohen en población general española.Métodos. El test fue administrado a 211 personas (63,3 %mujeres) sanas de entre 19 y 70 años de edad. Usamos matricestetracóricas para obtener la fiabilidad test-retest y la consistencia interna. Se realizó un análisis factorial confirmatorio paracomprobar la unidimensionalidad del test. Utilizamos correlaciones de Pearson para examinar asociaciones entre variables.Resultados. La media en el estudio fue de 18 (DE = 1,38).Se obtuvo un alfa de Cronbach de 0,75. Calculamos los índices Guttman Lambda 3 para cada ítem. 17 de 20 ítems obtuvieron una estabilidad test-retest excelente. No encontramosasociaciones entre el rendimiento y el género, la edad o elnivel académico. El test presentó una estructura unidimensional (CFI = 0,889; TLI = 0,873 y RMSEA = 0,047).Conclusiones. El Test de Caras de Baron Cohen puede serútil como instrumento de medida a pesar de no ser sensibleal género y a la edad. Puesto que presenta un efecto techo,no resulta un instrumento adecuado para obtener medidasprecisas del funcionamiento superior de esta habilidad. (AU)

Introduction: Facial emotion recognition is consideredthe foundation of effective social functioning, but it hasbeen found impaired in several clinical populations. However, there are few validated tests to measure the ability. Tothe best of our knowledge, there is no validated measurein a Spanish population. We translated and validated BaronCohen’s Face Test in a general Spanish population.Methods. The test was administered to 211 (63.3% female) healthy volunteers between 19 and 70 years of age. Weused tetrachoric matrices to obtain item per item test-retestreliability and internal consistency. We used confirmatoryfactor analysis to test for unidimensionality. We used Pearson correlations to examine associations between variables.Results. The mean score was 18 (SD=1.38). Cronbach’salfa was 0.75. Guttman Lambda 3 indexes yielded 17 outof 20 items to have excellent test-retest reliability. Gender or age differences in performance were not found. Thetest seems to comply with a one-dimensional structure:CFI=0.889; TLI=0.873 and RMSEA=0.047.Conclusions. Baron Cohen’s Face Test could be a validmeasure of FER, although it is not sensitive to age or gender.Because it presents a certain ceiling effect, it could not beappropriate to detect excelling performance. (AU)

Psychiatric comorbidities in autism spectrum disorder: A comparative study between DSM-IV-TR and DSM-5 diagnosis / Comorbilidades psiquiátricas en los trastornos del espectro autista: estudio comparativo entre los criterios DSM-IV-TR y DSM-5

Background/Objective: The heterogeneous clinical presentations of individuals with Autism Spectrum Disorders (ASD) pose a significant challenge for sample characterization. Therefore the main goal of DSM-5 must be to identify subgroups of ASD, including comorbidity disorders and severity. The main goal of this study is to explore the psychiatric comorbidities and the severity of symptoms that could be relevant for the phenotype characterization in ASD and also to compare these results according to the different classification criteria between the DSM-IV-TR and the DSM-5. Method: A comparative study of severity and psychiatric comorbidities was carried out between a sample of participants that only met criteria for Pervasive Developmental Disorder (PDD) according to the DSM-IV-TR and a sample of participants that also met ASD criteria according to DSM-5 classification. The recruitment of children was via educational (N=123). The psychiatric symptoms, comorbid disorders and severity of symptoms were assessed through The Nisonger Child Behavior Rating Form, clinical interview and The Inventory of Autism Spectrum Disorder, respectively. The psychiatric comorbidities considered were: anxiety, eating behavioural problems, self-aggressiveness, hetero-aggressiveness, self-harm, obsessive compulsive disorder and attention deficit and hyperactivity disorder. Results: Statistically significant differences between both groups were found regarding obsessive compulsive disorder, eating behavioural problems and severity. Conclusions: The results support the hypothesis that patients who meet the DSM-5 criteria have more severe symptoms, not only regarding the core autistic symptoms but also in relation with psychiatric comorbidities (AU)

Antecedentes/Objetivo: Los Trastornos del Espectro Autista (TEA) incluyen un grupo heterogéneo en cuanto a su presentación clínica, que supone un desafío a nivel de caracterización diagnóstica. Por consiguiente, el objetivo principal de la clasificación DSM-5 debería de ser identificar subgrupos de TEA incluyendo severidad y comorbilidades psiquiátricas. El objetivo principal de este estudio es explorar las comorbilidades diagnósticas que pueden ser relevantes como descriptores de fenotipos autistas así como la severidad de los síntomas de autismo y comparar los resultados de las diferentes criterios de clasificación entre el DSM-IV-TR y el DSM-5. Método: Se realiza un estudio comparativo de severidad y comorbilidades psiquiátricas entre una muestra con diagnóstico de Trastorno Generalizado del Desarrollo, según criterios DSM-IV-TR, y una muestra que cumplía también criterios para TEA según la clasificación DSM-5. La muestra fue obtenida en centros educativos (N=123). Las comorbilidades psiquiátricas y la severidad de los síntomas se evaluaron a través del The Nisonger Child Behavior Rating Form, entrevista clínica y el Inventario de Trastorno del Espectro Autista, respectivamente. Las comorbilidades estudiadas fueron ansiedad, alteraciones de la conducta alimentaria, auto-agresividad, hetero-agresividad, autolesiones, trastorno obsesivo-compulsivo y déficit de atención e hiperactividad. Resultados: Se encontraron diferencias estadísticamente significativas entre ambos grupos para trastorno obsesivo-compulsivo, alteraciones de la conducta alimentaria y severidad. Conclusiones: Se apoya la hipótesis de que los individuos que cumplen criterios diagnósticos según DSM-5 tienen mayor severidad sintomática, no sólo con respecto a los síntomas autistas centrales, sino también en relación con comorbilidades psiquiátricas (AU)

Study of positive and negative feedback sensitivity in psychosis using the Wisconsin Card Sorting Test.

BACKGROUND: Schizophrenia involves marked motivational and learning deficits that may reflect abnormalities in reward processing. The purpose of this study was to examine positive and negative feedback sensitivity in schizophrenia using computational modeling derived from the Wisconsin Card Sorting Test (WCST). We also aimed to explore feedback sensitivity in a sample with bipolar disorder. METHODS: Eighty-three individuals with schizophrenia and 27 with bipolar disorder were included. Demographic, clinical and cognitive outcomes, together with the WCST, were considered in both samples. Computational modeling was performed using the R syntax to calculate 3 parameters based on trial-by-trial execution on the WCST: reward sensitivity (R), punishment sensitivity (P), and choice consistency (D). The associations between outcome variables and the parameters were investigated. RESULTS: Positive and negative sensitivity showed deficits, but P parameter was clearly diminished in schizophrenia. Cognitive variables, age, and symptoms were associated with R, P, and D parameters in schizophrenia. The sample with bipolar disorder would show cognitive deficits and feedback abnormalities to a lesser extent than individuals with schizophrenia. CONCLUSION: Negative feedback sensitivity demonstrated greater deficit in both samples. Idiosyncratic cognitive requirements in the WCST might introduce confusion when supposing model-free reinforcement learning. Negative symptoms of schizophrenia were related to lower feedback sensitivity and less goal-directed patterns of choice.

Executive function is affected in autism spectrum disorder, but does not correlate with intelligence.

INTRODUCTION: Studies of executive function in autism spectrum disorder without intellectual disability (ASD-WID) patients are contradictory. We assessed a wide range of executive functioning cognitive domains in a sample of children and adolescents with ASD-WID and compared them with age-, sex-, and intelligence quotient (IQ)-matched healthy controls. METHODS: Twenty-four ASD-WID patients (mean age 12.8±2.5 years; 23 males; mean IQ 99.20±18.81) and 32 healthy controls (mean age 12.9±2.7 years; 30 males; mean IQ 106.81±11.02) were recruited. RESULTS: Statistically significant differences were found in all cognitive domains assessed, with better performance by the healthy control group: attention (U=185.0; P=.0005; D=0.90), working memory (T51.48=2.597; P=.006; D=0.72), mental flexibility (U=236.0; P=.007; D=0.67), inhibitory control (U=210.0; P=.002; D=0.71), and problem solving (U=261.0; P=0.021; D=0.62). These statistically significant differences were also found after controlling for IQ. CONCLUSION: Children and adolescents with ASD-WID have difficulties transforming and mentally manipulating verbal information, longer response latency, attention problems (difficulty set shifting), trouble with automatic response inhibition and problem solving, despite having normal IQ. Considering the low executive functioning profile found in those patients, we recommend a comprehensive intervention including work on non-social problems related to executive cognitive difficulties.

Age at First Episode Modulates Diagnosis-Related Structural Brain Abnormalities in Psychosis.

Brain volume and thickness abnormalities have been reported in first-episode psychosis (FEP). However, it is unclear if and how they are modulated by brain developmental stage (and, therefore, by age at FEP as a proxy). This is a multicenter cross-sectional case-control brain magnetic resonance imaging (MRI) study. Patients with FEP (n = 196), 65.3% males, with a wide age at FEP span (12-35 y), and healthy controls (HC) (n = 157), matched for age, sex, and handedness, were scanned at 6 sites. Gray matter volume and thickness measurements were generated for several brain regions using FreeSurfer software. The nonlinear relationship between age at scan (a proxy for age at FEP in patients) and volume and thickness measurements was explored in patients with schizophrenia spectrum disorders (SSD), affective psychoses (AFP), and HC. Earlier SSD cases (ie, FEP before 15-20 y) showed significant volume and thickness deficits in frontal lobe, volume deficits in temporal lobe, and volume enlargements in ventricular system and basal ganglia. First-episode AFP patients had smaller cingulate cortex volume and thicker temporal cortex only at early age at FEP (before 18-20 y). The AFP group also had age-constant (12-35-y age span) volume enlargements in the frontal and parietal lobe. Our study suggests that age at first episode modulates the structural brain abnormalities found in FEP patients in a nonlinear and diagnosis-dependent manner. Future MRI studies should take these results into account when interpreting samples with different ages at onset and diagnosis.

Psychiatric comorbidities in autism spectrum disorder: A comparative study between DSM-IV-TR and DSM-5 diagnosis.

Background/Objective: The heterogeneous clinical presentations of individuals with Autism Spectrum Disorders (ASD) pose a significant challenge for sample characterization. Therefore the main goal of DSM-5 must be to identify subgroups of ASD, including comorbidity disorders and severity. The main goal of this study is to explore the psychiatric comorbidities and the severity of symptoms that could be relevant for the phenotype characterization in ASD and also to compare these results according to the different classification criteria between the DSM-IV-TR and the DSM-5. Method: A comparative study of severity and psychiatric comorbidities was carried out between a sample of participants that only met criteria for Pervasive Developmental Disorder (PDD) according to the DSM-IV-TR and a sample of participants that also met ASD criteria according to DSM-5 classification. The recruitment of children was via educational (N = 123). The psychiatric symptoms, comorbid disorders and severity of symptoms were assessed through The Nisonger Child Behavior Rating Form, clinical interview and The Inventory of Autism Spectrum Disorder, respectively. The psychiatric comorbidities considered were: anxiety, eating behavioural problems, self-aggressiveness, hetero-aggressiveness, self-harm, obsessive compulsive disorder and attention deficit and hyperactivity disorder. Results: Statistically significant differences between both groups were found regarding obsessive compulsive disorder, eating behavioural problems and severity. Conclusions: The results support the hypothesis that patients who meet the DSM-5 criteria have more severe symptoms, not only regarding the core autistic symptoms but also in relation with psychiatric comorbidities.

Antecedentes/Objetivo: Los Trastornos del Espectro Autista (TEA) incluyen un grupo heterogéneo en cuanto a su presentación clínica, que supone un desafío a nivel de caracterización diagnóstica. Por consiguiente, el objetivo principal de la clasificación DSM-5 debería de ser identificar subgrupos de TEA incluyendo severidad y comorbilidades psiquiátricas. El objetivo principal de este estudio es explorar las comorbilidades diagnósticas que pueden ser relevantes como descriptores de fenotipos autistas así como la severidad de los síntomas de autismo y comparar los resultados de las diferentes criterios de clasificación entre el DSM-IV-TR y el DSM-5. Método: Se realiza un estudio comparativo de severidad y comorbilidades psiquiátricas entre una muestra con diagnóstico de Trastorno Generalizado del Desarrollo, según criterios DSM-IV-TR, y una muestra que cumplía también criterios para TEA según la clasificación DSM-5. La muestra fue obtenida en centros educativos (N = 123). Las comorbilidades psiquiátricas y la severidad de los síntomas se evaluaron a través del The Nisonger Child Behavior Rating Form, entrevista clínica y el Inventario de Trastorno del Espectro Autista, respectivamente. Las comorbilidades estudiadas fueron ansiedad, alteraciones de la conducta alimentaria, auto-agresividad, hetero-agresividad, autolesiones, trastorno obsesivo-compulsivo y déficit de atención e hiperactividad. Resultados: Se encontraron diferencias estadísticamente significativas entre ambos grupos para trastorno obsesivo-compulsivo, alteraciones de la conducta alimentaria y severidad. Conclusiones: Se apoya la hipótesis de que los individuos que cumplen criterios diagnósticos según DSM-5 tienen mayor severidad sintomática, no sólo con respecto a los síntomas autistas centrales, sino también en relación con comorbilidades psiquiátricas.

Functional deterioration from the premorbid period to 2 years after the first episode of psychosis in early-onset psychosis.

The aim of the study was to analyze changes in functional adjustment from childhood to 2 years after the first episode of psychosis (FEP) in patients with early-onset schizophrenia spectrum disorders (SSD) and affective psychoses (AFP) and a good or intermediate level of premorbid adjustment. We followed 106 adolescents (aged 12-17 years) with FEP for 2 years after recruitment. Premorbid adjustment in childhood was assessed in 98 patients with the childhood subscale of the Cannon-Spoor Premorbid Adjustment Scale (c-PAS). Global functioning was assessed 2 years after the FEP with the Children's Global Assessment Scale (c-GAS) or the Global Assessment of Functioning scale (GAF), as appropriate. Functional deterioration was defined as a downward shift in the level of functional adjustment from childhood to 2 years after the FEP. In patients with good or intermediate premorbid adjustment, functional deterioration was observed in 28.2 % (26.5 % of the AFP group, 29.4 % of the SSD group). Longer duration of untreated psychosis (Beta = 0.01; P = 0.01) and higher symptom severity at the FEP, as measured with the Clinical Global Impression Scale (Beta = 1.12; P = 0.02), significantly predicted the presence of functional deterioration, accounting for 21.4 % of the variance. Irrespective of diagnosis (SSD or AFP), almost one-third of adolescents with FEP and good or intermediate premorbid adjustment showed functional deterioration from the premorbid period to 2 years after the FEP.

A longitudinal study on the relationship between duration of untreated psychosis and executive function in early-onset first-episode psychosis.

BACKGROUND: The relationship between duration of untreated psychosis (DUP) and executive function (EF) in patients with first-episode psychosis (FEP) is controversial. We aim to assess the influence of DUP on changes in EF over a 2-year period in subjects with early-onset FEP (first psychotic symptom before age 18) and less than 6 months of positive symptoms. METHODS: A total of 66 subjects were included in the study (19 females [28.8%], mean age 16.2 ± 1.6 years). The influence of DUP on changes in EF over the 2-year follow-up (expressed as a composite score of 5 cognitive abilities: attention, working memory, cognitive flexibility, response inhibition, and problem solving) was estimated using a multivariate linear regression model after removing the effect of intelligence quotient and controlling for age, gender, diagnosis, premorbid adjustment, severity of positive and negative symptoms at baseline, global functioning at baseline, and mean daily antipsychotic dosage during follow-up. RESULTS: Mean DUP was 65.0 ± 6.9 days (95% confidence interval [CI], 51.2, 78.8). Median DUP was 47.5 days (range 2-180 days). Negative symptoms at baseline was the only variable significantly associated with EF at baseline (10.9% of explained variance [e.v. 10.9%], p=0.007). Only shorter DUP (e.v. 8.7%, p=0.013) and greater severity of baseline negative symptoms (e.v. 10.0%, p=0.008) were significantly associated with greater improvement in EF. CONCLUSIONS: In early-onset FEP, shorter DUP was associated with greater improvement in EF over a 2-year follow-up period.

Duration of untreated psychosis predicts functional and clinical outcome in children and adolescents with first-episode psychosis: a 2-year longitudinal study.

Longer duration of untreated psychosis (DUP) in adult patients with first-episode psychosis (FEP) has been associated with poor clinical and social outcomes. We aimed to estimate the influence of DUP on outcome at 2-year follow-up in subjects with an early-onset (less than 18 years of age) FEP of less than 6 months' duration. A total of 80 subjects (31.3% females, mean age 16.0±1.8 years) were enrolled in the study. The influence of DUP on outcome was estimated using multiple regression models (two linear models for influence of DUP on the C-GAF at 2 years and C-GAF change through the follow-up period, and a logistic model for influence of DUP on 41 PANSS remission at 2 years in schizophrenia patients (n=47)). Mean DUP was 65.3±54.7 days. Median DUP was 49.5 days. For the whole sample (n=80), DUP was the only variable significantly related to C-GAF score at 2-year follow-up (Beta=-0.13, p<0.01), while DUP and premorbid adjustment (Beta=-0.01, p<0.01; and Beta=-0.09, p=0.04, respectively) were the only variables significantly related to C-GAF change. In schizophrenia patients, DUP predicted both C-GAF score at 2 years and C-GAF change, while in patients with affective psychosis (n=22), DUP was unrelated to outcome. Lower baseline C-GAF score (OR=0.91, p<0.01) and shorter DUP (OR=0.98, p=<0.01) were the only variables that significantly predicted clinical remission in schizophrenia patients. In conclusion, longer DUP was associated with lower C-GAF at 2 years, less increase in C-GAF, and lower rates of clinical remission in early-onset FEP. Our findings support the importance of early detection programs, which help shorten DUP.