One-shot platelet-rich plasma (PRP) injection is non-inferior to extracorporeal shockwave therapy in the management of supraspinatus tendinosis.

PURPOSE: Supraspinatus tendinosis (ST) refers to the intratendinous degeneration of the supraspinatus tendon. Platelet-Rich Plasma (PRP) is one of the possible conservative treatments for supraspinatus tendinosis. This prospective observational study aims to evaluate the efficacy and safety of a single ultrasound-guided PRP injection in the treatment of supraspinatus tendinosis and to assess its non-inferiority to the widely used shockwave therapy. METHODS: Seventy-two amateur athletes (35 male, mean age: 43.75 ± 10.82, range 21-58 years old) with ST were finally included in the study. All the patients underwent clinical evaluation at baseline, (T0) and at 1-month (T1), 3-month (T2) and 6-month (T3) follow-up using the following clinical scales: the Visual Analogue Scale for pain (VAS), Constant Score and the Disabilities of the Arm, Shoulder and Hand Score (DASH). A T0 and T3 ultrasound examination was also performed. The findings observed in the recruited patients were compared to the clinical results observed in a retrospective control group made up of 70 patients (32 male, mean age = 41.29 ± 13.85, range 20-65 years old) treated by extracorporeal shockwave therapy (ESWT). RESULTS: VAS, DASH and Constant scores significantly improved from T0 to T1; the improvement in clinical scores was kept until T3. No local nor systemic adverse events were observed. An improvement in the tendon structure was observed on ultrasound examination. PRP showed a non-statistical inferiority, in terms of efficacy and safety, compared to ESWT. CONCLUSION: The PRP one-shot injection is a valid conservative treatment to reduce pain, and improve both quality of life and functional scores in patients with supraspinatus tendinosis. Furthermore, the PRP intratendinous one-shot injection showed a non-inferiority in terms of efficacy at the 6-month follow-up, compared to ESWT.

Neurocognitive functioning in bulimia nervosa: the role of neuroendocrine, personality and clinical aspects.

BACKGROUND: Studies investigating neurocognitive impairment in subjects with eating disorders (EDs) have reported heterogeneous patterns of impairment and, in some instances, no dysfunction. The present study aimed to define the pattern of neurocognitive impairment in a large sample of bulimia nervosa (BN) patients and to demonstrate that neuroendocrine, personality and clinical characteristics influence neurocognitive performance in BN. METHOD: Attention/immediate memory, set shifting, perseveration, conditional and implicit learning were evaluated in 83 untreated female patients with BN and 77 healthy controls (HC). Cortisol and 17ß-estradiol plasma levels were assessed. Cloninger's Temperament and Character Inventory - Revised (TCI-R), the Bulimic Investigation Test Edinburgh (BITE) and the Montgomery-Asberg Depression Rating Scale (MADRS) were administered. RESULTS: No impairment of cognitive performance was found in subjects with BN compared with HC. Cortisol and 'Self-directedness' were associated with better performance on conditional learning whereas 17ß-estradiol had a negative influence on this domain; 'Reward dependence' was associated with worse performance on implicit learning; and depressive symptomatology influenced performance on the Wisconsin Card Sorting Test (WCST) negatively. CONCLUSIONS: No cognitive impairment was found in untreated patients with BN. Neuroendocrine, personality and clinical variables do influence neurocognitive functioning and might explain discrepancies in literature findings.

Predictors and moderators of time to remission of major depression with interpersonal psychotherapy and SSRI pharmacotherapy.

BACKGROUND: Although many studies suggest that, on average, depression-specific psychotherapy and antidepressant pharmacotherapy are efficacious, we know relatively little about which patients are more likely to respond to one versus the other. We sought to determine whether measures of spectrum psychopathology are useful in deciding which patients with unipolar depression should receive pharmacotherapy versus depression-specific psychotherapy. METHOD: A total of 318 adult out-patients with major depression were randomly assigned to escitalopram pharmacotherapy or interpersonal psychotherapy (IPT) at academic medical centers at Pittsburgh, Pennsylvania and Pisa, Italy. Our main focus was on predictors and moderators of time to remission on monotherapy at 12 weeks. RESULTS: Participants with higher scores on the need for medical reassurance factor of the Panic-Agoraphobic Spectrum Self-Report (PAS-SR) had more rapid remission with IPT and those with lower scores on the psychomotor activation factor of the Mood Spectrum Self-Report (MOODS-SR) experienced more rapid remission with selective serotonin reuptake inhibitor (SSRI) pharmacotherapy. Non-specific predictors of longer time to remission with monotherapy included several panic spectrum and mood spectrum factors and the Social Phobia Spectrum (SHY) total score. Higher baseline scores on the 17- and 25-item Hamilton Depression Rating Scales (HAMD-17 and HAMD-25) and the Work and Social Adjustment Scale (WSAS) also predicted a longer time to remission, whereas being married predicted a shorter time to remission. CONCLUSIONS: This exploratory study identified several non-specific predictors but few moderators of psychotherapy versus pharmacotherapy outcome. It offers useful indicators of the characteristics of patients that are generally difficult to treat, but only limited guidance as to who benefits from IPT versus SSRI pharmacotherapy.

Treatment-emergent suicidal ideation during 4 months of acute management of unipolar major depression with SSRI pharmacotherapy or interpersonal psychotherapy in a randomized clinical trial.

BACKGROUND: To date, few randomized controlled trials (RCTs) of major depression have examined suicidal ideation as an outcome measure. Our aim is to determine the incidence of treatment-emergent suicidal ideation (ESI) and behaviors during the acute phase of treatment with an SSRI antidepressant or interpersonal psychotherapy (IPT) in patients with unipolar major depression. METHODS: In a two-site RCT, 291 adult outpatients with nonpsychotic major depression and a Hamilton Depression Rating Scale (HDRS) score ≥15 were randomly allocated to IPT or SSRI. Participants who did not remit with monotherapy received augmentation with the other treatment. ESI was defined as a post-baseline HDRS suicidality item score ≥2 or a post-baseline Quick Inventory of Depressive Symptomatology (QIDS) score ≥2 in patients with a baseline score ≤1. RESULTS: Of the 231 participants who had no suicidal ideation at baseline, 32 (13.8%) subsequently exhibited ESI on at least one post-baseline visit. Time to suicidal ideation was significantly longer in patients allocated to SSRI compared to those allocated to IPT (HR = 2.21, 95% CI 1.04-4.66, P = .038), even after controlling for treatment augmentation, benzodiazepine use, and comorbidity with anxiety disorders. Worsening of suicidal ideation occurred in 7/60 patients who had suicidal ideation at baseline. In the large majority of cases, suicidal ideation was successfully managed with the study protocol. CONCLUSIONS: In the context of careful monitoring and frequent contact, selective serotonin reuptake inhibitor (SSRI) was associated with a lower risk of ESI than IPT and both SSRI and IPT appeared to be safe treatments for patients with past suicide attempts, none of whom exhibited ESI during the study.

Sick leave request following anti-COVID-19 vaccine administration is low among healthcare workers: results from a retrospective cross-sectional monocentric study.

OBJECTIVE: Anti-COVID-19 vaccines were mainly associated with non-serious adverse events (AEs), whose prevalence was reported to be up to 70% in healthcare workers (HCWs). This may lead to sick leave requests, but this impact has never been quantified. This study aimed to investigate the absence from work among HCWs following anti-COVID-19 vaccination. Its association with age and previous COVID-19 infection was also assessed. PATIENTS AND METHODS: This is a retrospective observational cross-sectional study on administrative data about sick leave requests after anti-COVID-19 vaccination. All the HCWs employed at the Niguarda Hospital (Milan, Italy) who received the vaccine from December 27, 2020 to February 28, 2021 were included. RESULTS: In total, 4,088 HCWs received the first dose of the vaccine and 4,043 completed the vaccination cycle. After the first injection, 1.6% of HCWs requested sick leave, while after the second injection, the number of requests significantly increased (+6.1%, p<0.001). A significant increase in sick leave was detected for those who have had SARS-CoV-2 infection after the first injection (+2.3%, p<0.001). After the second dose, a significant increase in sick leave was observed in the 20-30-year-old group compared to >30 years (+3.6%, p=0.017), if HCWs without a history of SARS-CoV-2 infection were considered. CONCLUSIONS: The requests for sick leave among HCWs following the anti-COVID-19 vaccine were limited and higher after the second injection. This may help the management of the human resources when the large-scale administration of the anti-COVID-19 vaccines will involve other categories of workers.

Frequency and clinical correlates of adult separation anxiety in a sample of 508 outpatients with mood and anxiety disorders.

OBJECTIVE: To evaluate the frequency and clinical correlates of adult separation anxiety disorder in a large cohort of patients with mood and anxiety disorders. METHOD: Overall, 508 outpatients with anxiety and mood disorders were assessed by the structured clinical interview for diagnostic and statistical manual (IV edition) axis I disorders for principal diagnosis and comorbidity and by other appropriate instruments for separation anxiety into adulthood or childhood. RESULTS: Overall, 105 subjects (20.7%) were assessed as having adult separation anxiety disorder without a history of childhood separation anxiety and 110 (21.7%) had adult separation anxiety disorder with a history of childhood separation anxiety. Adult separation anxiety was associated with severe role impairment in work and social relationships after controlling for potential confounding effect of anxiety comorbidity. CONCLUSION: Adult separation anxiety disorder is likely to be much more common in adults than previously recognized. Research is needed to better understand the relationships of this condition with other co-occurring affective disorders.

The structure of lifetime panic-agoraphobic spectrum.

The heterogeneity of the clinical presentation of panic disorder (PD) has prompted researchers to describe different subtypes of PD, on the basis of the observed predominant symptoms constellation. Starting from a dimensional approach to panic disorder, an instrument to assess lifetime panic-agoraphobic spectrum (PAS) available in interview or self-report form (SCI-PAS, PAS-SR) was developed which proved to have sound psychometric properties and the ability to predict delayed response to treatment in patients with mood disorders. However, the structure of the instrument was defined a priori and an examination of its empirical structure is still lacking. Aim of the present report is to analyse the factor structure of the PAS taking advantage of a large database of subjects with panic disorders (N=630) assessed in the framework of different studies. Using a classical exploratory factor analysis based on a tetrachoric correlation matrix and oblique rotation, 10 factors were extracted, accounting overall for 66.3% of the variance of the questionnaire: panic symptoms, agoraphobia, claustrophobia, separation anxiety, fear of losing control, drug sensitivity and phobia, medical reassurance, rescue object, loss sensitivity, reassurance from family members. The first two factors comprise the DSM-IV criteria for panic disorder and agoraphobia. The other factors had received limited empirical support to date. We submit that these symptoms profiles might be clinically relevant for tailoring drug treatments or psychotherapeutic approaches to specific needs. Future perspectives might include the use of these factors to select homogeneous subgroups of patients for brain-imaging studies and to contribute to elucidating the causes and pathophysiology of panic disorder at molecular level.

Metabolic syndrome in Argentinean patients with systemic lupus erythematosus.

The objective was to determine the prevalence of the metabolic syndrome (MS) in patients with systemic lupus erythematosus (SLE) in Argentina, to assess the factors associated to it, and to compare the results with a control group with non-inflammatory disorders. The study included 147 patients with SLE and 119 controls. MS was defined according to criteria by the American Heart Association/National Heart, Lung, and Blood Institute (AHA/NHLBI) Scientific Statement. Demographic characteristics, Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) and Systemic Lupus International Collaborating Clinics/ACR Damage Index (SDI) were assessed as well as administration, maximum dose and cumulative dose of prednisone and hydroxychloroquine (HCQ). MS prevalence was 28.6% (CI 95%: 21.4-36.6) in patients with SLE and 16% in controls (P = 0.0019). Patients with SLE presented higher arterial hypertension frequency compared with controls (43 vs 25%, P = 0.007). When comparing lupus patients with MS (n = 41) and without MS (n = 106), no significant differences were observed regarding duration of the disease, SLEDAI or cumulative prednisone dose. Cumulative damage was associated independently with MS (OR 1.98; P = 0.021), whereas HCQ use was found to be protective (OR 0.13; P = 0.015). Patients with lupus presented higher MS prevalence than controls with non-inflammatory disorders, and occurrence of arterial hypertension was also higher. MS was associated with cumulative damage; the use of HCQ showed to be protective against presence of MS.

The structure of lifetime manic-hypomanic spectrum.

BACKGROUND: The observation that bipolar disorders frequently go unrecognized has prompted the development of screening instruments designed to improve the identification of bipolarity in clinical and non-clinical samples. Starting from a lifetime approach, researchers of the Spectrum Project developed the Mood Spectrum Self-Report (MOODS-SR) that assesses threshold-level manifestations of unipolar and bipolar mood psychopathology, but also atypical symptoms, behavioral traits and temperamental features. The aim of the present study is to examine the structure of mania/hypomania using 68 items of the MOODS-SR that explore cognitive, mood and energy/activity features associated with mania/hypomania. METHODS: A data pool of 617 patients with bipolar disorders, recruited at Pittsburgh and Pisa, Italy was used for this purpose. Classical exploratory factor analysis, based on a tetrachoric matrix, was carried out on the 68 items, followed by an Item Response Theory (IRT)-based factor analytic approach. RESULTS: Nine factors were initially identified, that include Psychomotor Activation, Creativity, Mixed Instability, Sociability/Extraversion, Spirituality/Mysticism/Psychoticism, Mixed Irritability, Inflated Self-esteem, Euphoria, Wastefulness/Recklessness, and account overall for 56.4% of the variance of items. In a subsequent IRT-based bi-factor analysis, only five of them (Psychomotor Activation, Mixed Instability, Spirituality/Mysticism/Psychoticism, Mixed Irritability, Euphoria) were retained. CONCLUSIONS: Our data confirm the central role of Psychomotor Activation in mania/hypomania and support the definitions of pure manic (Psychomotor Activation and Euphoria) and mixed manic (Mixed Instability and Mixed Irritability) components, bearing the opportunity to identify patients with specific profiles for a better clinical and neurobiological definition.

Risk factors for postpartum depression: the role of the Postpartum Depression Predictors Inventory-Revised (PDPI-R). Results from the Perinatal Depression-Research & Screening Unit (PNDReScU) study.

The aims of this study were to identify the frequency of the risk factors for postpartum depression (PPD) listed in the Postpartum Depression Predictors Inventory-Revised (PDPI-R) during pregnancy and 1 month after delivery and to determine the predictive validity of the PDPI-R. The study used a prospective cohort design. Women completed the PDPI-R at the 3rd and the 8th months of pregnancy and at the 1st month after childbirth. Women were prospectively followed across three different time points during the postpartum using Structured Clinical Interview for DSM-IV Disorders to determine the presence of major or minor depression. The prenatal version of the PDPI-R administered at two different time points during pregnancy predicted accurately 72.6% and 78.2% of PPD and the full version administered at the 1st month after delivery predicted 83.4% of PPD. The cutoffs identified were 3.5 for the prenatal version and 5.5 for the full version. The PDPI-R is a useful and a valid screening tool for PPD.

Gender moderates the relationship between mania spectrum and serotonin transporter polymorphisms in depression.

The short (s) variant of the serotonin transporter gene linked functional polymorphic region (5-HTTLPR) is associated with depression. Stressful life events, gender, and race have been shown to moderate this association. Because features of mania/hypomania seem to constitute an indicator of higher severity of depression, we examined the relationship between 5-HTTLPR genotype and symptoms of mania-hypomania spectrum occurring over the lifetime in patients with major depression. The possible moderating role of gender in this relationship was taken into account. Two hundred twenty-two patients with unipolar major depression were genotyped for 5-HTTLPR and nine other representative polymorphisms, and were administered the Mood Spectrum Questionnaire, Lifetime Version (MOODS-SR). The manic-hypomanic (MH) component score was used for analysis. Using a linear model of the MH score as a function of genotypes and gender, controlling for age, severity of depression, and site, we found significant effects of gender (F = 8.003, df = 1, P = 0.005), of the interaction gender x genotype (F = 4.505, df = 2, P = 0.012), and of the baseline Hamilton score (F = 5.404, df = 1, P = 0.021), non-significant effects of genotype (F = 1.298, df = 2, P = 0.275), age (F = 0.310, df = 1, P = 0.578) site (F = 0.504, df = 1, P = 0.479). Significant associations were also detected at three other SNPs. The association between the manic/hypomanic component of the MOODS-SR and the polymorphisms of the 5-HTTLPR is moderated by gender. This finding is intriguing from a clinical point of view because women with unipolar disorder and the "ss" genotype seem to constitute a sub-group with higher severity of depression. These results should be considered tentative pending replication in other samples.

How many Na+-dependent carriers for L-alanine and L-proline in the eel intestine? Studies with brush-border membrane vesicles.

Using brush-border membrane (BBM) vesicles prepared from the intestine of the European eel, the specificity of L-alanine and L-proline Na+-dependent transport was investigated by measuring the uptake of isotopically labelled substrates. In the presence of Na+ ions, cross-inhibition between alanine and proline transports was observed; in addition alpha-(methylamino)isobutyric acid (MeAIB) inhibited proline but had no effect on alanine uptake. These results can be explained by the presence, in eel intestinal BBM vesicles, of at least two distinct agencies for Na+-dependent proline and alanine translocation. The first system is specific for alanine and short-chain neutral amino acids; the second system, specific for imino acids and the N-methylated analogues, is regulated by alanine concentration.

The Na(+)-dependent proline carrier, of eel intestinal brush-border membrane, sequentially binds proline and then Na+.

The mechanism of Na+/L-proline cotransport, present on brush-border membrane (BBM) vesicles of the European eel intestine, was studied. Initial cotransport rates, depending on increasing proline and Na+ concentrations in the extravesicular medium (zero-trans conditions), were measured by monitoring the decay of an inside-negative membrane potential, i.e. the fluorescence quenching of the voltage-sensitive cyanine dye 3,3'-diethylthiacarbocyanine iodide (DiS-C2(5)). By simultaneously estimating the substrate-dependent Na(+)-influx (with the fluorescent dye) and the Na(+)-dependent [3H]substrate influx, it was concluded that proline was cotransported with 1 Na+ ion and glucose with 2 Na+ ions. The kinetics of proline/Na+ cotransport were then investigated. Graphical analysis excluded a ping-pong mechanism. Under rapid equilibrium assumptions, by fitting model equations to rate values it was possible to exclude the random and the ordered Na+/proline mechanisms. Therefore, in eel intestinal BBM vesicles, the mechanism of proline/Na+ cotransport is ordered and prolineout binds to the carrier prior to Na+out.

The psychotic spectrum: validity and reliability of the Structured Clinical Interview for the Psychotic Spectrum.

This study evaluates the validity and the reliability of a new instrument developed to assess the psychotic spectrum: the Structured Clinical Interview for the Psychotic Spectrum (SCI-PSY). The instrument is based on a spectrum model that emphasizes soft signs, low-grade symptoms, subthreshold syndromes, as well as temperamental and personality traits comprising the clinical and subsyndromal psychotic manifestations. The items of the interview include, in addition to a subset of the DSM-IV criteria for psychotic syndromes, a number of features derived from clinical experience and from a review of the phenomenological descriptions of psychoses. Study participants were enrolled at 11 Italian Departments of Psychiatry located at 9 sites and included 77 consecutive patients with schizophrenia or schizoaffective disorder, 66 with borderline personality disorder, 59 with psychotic mood disorders, 98 with non-psychotic mood disorders and 57 with panic disorder. A comparison group of 102 unselected controls was enrolled at the same sites. The SCI-PSY significantly discriminated subjects with any psychiatric diagnosis from controls and subjects with from those without psychotic disorders. The hypothesized structure of the instrument was confirmed empirically.

Expression and immunolocalization of the aquaporin-8 water channel in rat gastrointestinal tract.

A remarkable amount, of water is transported in the gastrointestinal (GI) organs to fulfil the secretory and absorptive functions of the GI tract. However, the molecular basis of water movement in the GI epithelial barriers is still poorly known. Important clues about the mechanisms by which water is transported in the GI tract were provided by the recent identification of multiple aquaporin water channels expressed in GI tissues. Here we define the mRNA and protein expression and the cellular and subcellular distribution of aquaporin-8 (AQP8) in the rat GI tract. By semi-quantitative RT-PCR the AQP8 mRNA was detected in duodenum, proximal jejunum, proximal colon, rectum, pancreas and liver and, to a lesser extent, in stomach and distal colon. Immunohistochemistry using affinity-purified antibodies revealed AQP8 staining in the absorptive epithelial cells of duodenum, proximal jejunum, proximal colon and rectum where labeling was largely intracellular and confined to the subapical cytoplasm. Confirming previous results, AQP8 staining was seen at the apical pole of pancreatic acinar cells. Interestingly, both light and immunoelectron microscopy analyses showed AQP8 reactivity in liver where labeling was associated to hepatocyte intracellular vesicles and over the plasma membrane delimiting the bile canaliculi. A complex pattern was observed by immunoblotting with total membranes of the above GI organs incubated with affinity-purified anti-AQP8 antibodies which revealed multiple bands with molecular masses ranging between 28 and 45 kDa. This immunoblotting pattern was not modified after deglycosylation with N-glycosidase F except the 34-kDa band of liver that, as already reported, was partially down-shifted to 28 kDa. No bands were detected after preadsorption of the anti-AQP8 antibodies with the immunizing peptide. The cellular and subcellular distribution of AQP8 suggest physiological roles for this aquaporin in the absorption of water in the intestine and the secretion of bile and pancreatic juice in liver and pancreas, respectively. The large intracellular expression of AQP8 may indicate its recycling between the cytoplasmic compartment and the plasma membrane. The cytoplasmic localization observed may also relate to the involvement of AQP8 in processes of intracellular osmoregulation.

Abnormal peripheral benzodiazepine receptor density associated with generalized social phobia.

BACKGROUND: Peripheral benzodiazepine receptors (PBRs) are involved in regulating stress responses. Abnormally low numbers of platelet PBRs have been found in patients with panic disorder, posttraumatic stress disorder, and generalized anxiety disorder, but not in patients with obsessive-compulsive disorder (OCD) or major depressive disorder (MDD). The purpose of this study was to evaluate the PBR density on platelets from patients with generalized social phobia (GSP). METHODS: The density (Bmax) and dissociation constant (Kd) of platelet PBRs was determined for 53 medication-free patients with GSP and an equal number of control subjects (NC). RESULTS: The GSP group was found to have a significantly lower PBR Bmax than the NC group (GSP = 2764 +/- 1242 vs. NC = 4327 +/- 1850 fmol/mg protein, df = 1,100, F = 22.7, p = .00001). CONCLUSIONS: GSP shares this PBR abnormality with some other anxiety disorders but not with OCD or MDD. PBRs may play a role in the pathophysiology of some anxiety disorders.

Immunological alterations in adult obsessive-compulsive disorder.

BACKGROUND: Some recent findings suggest the involvement of autoimmune mechanisms in childhood onset of obsessive-compulsive disorder (OCD), on the basis of a parallel drawn with Sydenham's chorea, a manifestation of rheumatic fever. A monoclonal antibody called D8/D17 characterizing a B-lymphocyte antigen, present in almost all patients with rheumatic fever, has been found also in children affected by OCD, Tourette syndrome, and chronic tics to a greater degree than in healthy control subjects. The few observations of disturbances of some immunologic parameters in adult OCD patients, prompted the authors to investigate and compare subsets of peripheral immunological cells for differences in adult patients with OCD and healthy control subjects. METHODS: Twenty patients suffering from OCD, with no comorbidity for other psychiatric disorders, were compared with a similar group of healthy control subjects. The immune subsets were measured by flow cytometry. RESULTS: The CD8+ lymphocytes were significantly increased and CD4+ lymphocytes significantly decreased in OCD patients, while the other cells did not differ between the two groups. No correlation was found between immunologic and clinical parameters. CONCLUSIONS: These data indicate that patients with adult OCD showed increased CD8+, i.e., suppressor T lymphocytes, and decreased CD4+, which identify helper T lymphocytes, as compared with a similar group of healthy control subjects. The findings appear peculiar to patients with OCD and are suggestive of an immunologic imbalance, which might be related to the stress deriving from the frustrating situation determined by the disorder itself.

Regulation of the platelet serotonin transporter by protein kinase C in the young and elderly.

BACKGROUND: Some data show that different factors may influence the serotonin (5-HT) uptake rate. Our study aimed at evaluating the possible role of a protein kinase C (PKC) activator, i.e., 4-beta-12-tetradecanoylphorbol-13-acetate (beta-TPA) on the platelet 5-HT uptake of young and elderly subjects, through the measurement of the 5-HT uptake itself and 3H-paroxetine ([3H]PAR) binding sites, which correspond to the transporter protein. METHODS: Human platelets and 5-HT uptake were evaluated according to the method of Arora and Meltzer, while [3H]PAR binding was performed following the Marazziti et al method. RESULTS: The results showed that beta-TPA reduced significantly the maximal velocity (Vmax) of 5-HT uptake, with no change in the Michaelis constant or in [3H]PAR binding parameters, in platelets of both young and elderly subjects. Although this last group of subjects had a significantly lower Vmax than the other, the degree of inhibition was almost the same (75%) in both. CONCLUSIONS: These findings indicate that PKC decreases the 5-HT uptake rate by modifying the phosphorylation state of the transporter and with no change in the number of [3H]PAR binding sites. The responsiveness of this pathway is identical in both young and elderly subjects.

No coding variant of the tryptophan hydroxylase gene detected in seasonal affective disorder, obsessive-compulsive disorder, anorexia nervosa, and alcoholism.

BACKGROUND: The goal of this study was to evaluate the role of genetic variation in the coding sequence of tryptophan hydroxylase (TPH) in the pathogenesis of several psychiatric diseases in which altered serotonin function has been implicated: bipolar affective disorder (BP), obsessive-compulsive disorder (OCD), anorexia nervosa (AN), seasonal affective disorder (SAD), panic disorder (PD), and alcoholism (Alc). METHODS: Ninety-three percent of the TPH coding sequence was screened by polymerase chain reaction single-strand conformation polymorphism (SSCP) for DNA sequence variations in 128 AN, 88 OCD, 72 SAD, 45 PD, and 36 BP patients and 142 normal volunteers. Also included in the screening were 61 Alc randomly selected from a Finnish alcoholic population in which an association of a TPH intron 7 polymorphism with suicidality was previously observed. Polymorphisms detected by SSCP were characterized by DNA sequencing and by allele-specific restriction enzyme digestion. Genotyping was then performed in 34 Finnish alcoholic suicide attempters. RESULTS: A rare silent mutation was identified in exon 10 and is designated T1095C. The C1095 allele was found in 1 OCD and in 2 AN subjects; all 3 individuals were heterozygous (C1095/T1095) for the variant allele. No association was observed between this TPH T1095C variant with either OCD, AN, Alc, or suicidality. CONCLUSION: These results suggest that the coding sequence of the TPH gene does not contain abundant variants, and may not play a major role in vulnerability to several psychopathologies in which reduced serotonin turnover has been implicated.