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A meta-analysis of controlled studies on prevalence of eating disorders in Type 1 diabetes was performed in order to assess differences between diabetic and non-diabetic female subjects. All controlled studies using the Diagnostic and Statistical Manual of Mental Disorders Third Edition Revised (DSM Ill-R) or the DSM Fourth Edition (DSM IV) criteria for interview-based diagnosis were included in the analysis. The total sample was composed of 748 and 1587 female subjects with and without diabetes, respectively. The prevalence of anorexia nervosa (AN) in Type 1 diabetic subjects was not significantly different from that of controls (0.27 vs 0.06%), while that of bulimia nervosa and of the two conditions combined was significantly higher in diabetic patients (1.73 vs 0.69%, and 2.00 vs 0.75%, respectively; both p < 0.05). Type 1 diabetes is associated with a higher prevalence of bulimia nervosa in females.

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OBJECTIVE: Visual-spatial and executive functions deficits have been reported in obsessive-compulsive disorder (OCD). We investigated their specificity comparing cognitive function in OCD, panic disorder with agoraphobia (PD/A) and controls by a comprehensive neuropsychological battery. METHOD: Fifty-five subjects (25 OCD, 15 PD/A, 15 controls) without current depressive episode underwent structured clinical interview for DSM-IV, Yale-Brown Obsessive Compulsive Scale, Hamilton Anxiety Rating Scale, Hamilton Depression Rating Scale. Neuropsychological battery assessed: executive functions, visual discrimination, spatial memory and learning, verbal memory, general intellectual functioning. RESULTS: OCD showed controlled fluency, visual-spatial construction, learning and memory deficits; PD/A spatial learning impairment. OCD was discriminated from PD/A and controls by three tests scores, predicting group membership for 76.4% of the cases. CONCLUSION: Visual-constructive and controlled fluency deficits seem specific in OCD, while the spatial learning deficit, shared with PD patients, may not be disorder-specific, but anxiety-related. Results support the proposed ventral frontal-striatal circuit involvement in OCD.

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BACKGROUND: In 1994, the American Association on Mental Retardation with the DSM-IV has come to a final definition of pervasive developmental disorders (PDD), in agreement with the ICD-10. Prevalence of PDD in the general population is 0.1-0.15% according to the DSM-IV. PDD are more frequent in people with severe intellectual disability (ID). There is a strict relationship between ID and autism: 40% of people with ID also present a PDD, on the other hand, nearly 70% of people with PDD also have ID. We believe that in Italy PDD are underestimated because there is no agreement about the classification system and diagnostic instruments. METHOD: Our aim is to assess the prevalence of PDD in the Italian population with ID. The Scale of Pervasive Developmental Disorder in Mentally Retarded Persons (PDD-MRS) seems to be a very good instrument for classifying and diagnosing PDD. RESULTS: The application of the PDD-MRS and a clinical review of every individual case on a sample of 166 Italian people with ID raised the prevalence of PDD in this population from 7.8% to 39.2%. CONCLUSIONS: The study confirms the relationship between ID and autism and suggests a new approach in the study of ID in order to elaborate a new integrated model for people with ID.

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OBJECTIVE: Aim of this study was the assessment of the prevalence of eating disorders, and of eating disorder symptoms, in obese patients with type 2 diabetes, compared to non-diabetic subjects. DESIGN: Three samples of individuals were studied: a series of 156 (76 male, 80 female) overweight and obese type 2 diabetic patients, aged 30-65 y, with a body mass index (BMI)>28 kg/m(2) (DM); a series of 192 (20 male, 172 female) obese (BMI>30 kg/m(2)) non-diabetic patients aged 30-65 y seeking treatment for weight loss (OC); and a non-clinical sample of 48 (22 male, 26 female) obese (BMI>30 kg/m(2)) subjects aged 30-65 y selected from the lists of two general practices (OP). Eating behavior was assessed using the Eating Disorder Examination (EDE 12.0D). RESULTS: The prevalence of Binge Eating Disorder was lower than 5% in all the three samples. Median EDE scores in females were significantly higher in OC (3.0) and OP (3.4) than in DM (1.7), while diabetic patients showed higher scores on Restraint than both non-diabetic samples. Among diabetic patients, a significant correlation of EDE scores with HbA(1)c was observed. CONCLUSIONS: Type 2 diabetes is unlikely to induce relevant eating disturbances in obese patients, apart from an increase in restraint. Abnormalities of eating attitudes and behavior are associated with an impairment of metabolic control.

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Bipolar disorder is a common, lifelong condition that can present during childhood, adolescence, adulthood or later in life. It may occur alone but, more frequently, is complicated by comorbid psychiatric and medical disorders. As such, bipolar disorder presents in many different special populations, each of which warrants specific considerations of diagnosis, treatment and management. This review summarizes common issues concerning recognition of bipolar disorder, particularly in younger patients, discusses the prevalence and treatment of anxious disorder and addictive comorbidity, and considers bipolar disorder in the institutionalized and forensic populations. Treatment options and the supporting evidence are discussed.

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Dysthymia, as defined in the American Psychiatric Association and International Classification of Mental Disorders, refers to a prevalent form of subthreshold depressive pathology with gloominess, anhedonia, low drive and energy, low self-esteem and pessimistic outlook. Although comorbidity with panic, social phobic, and alcohol use disorders has been described, the most significant association is with major depressive episodes. Family history is loaded with affective, including bipolar, disorders. The latter finding explains why dysthymia, especially when onset is in childhood, can lead to hypomanic switches, both spontaneously and upon pharmacologic challenge in as many as 30%. Indeed, antidepressants from different classes -tricyclic antidepressants (TCAs), monoamine oxidase inhibitors (MAOIs), reversible inhibitors of monoamine oxidase A (RIMAs), selective serotonin-reuptake inhibitors (SSRIs) and, more recently, amisulpride, and spanning noradrenergic, serotonergic as well as dopaminergic mechanisms of action - have been shown to be effective against dysthymia in an average of 65% of cases. This is a promising development because social and characterologic disturbances so pervasive in dysthymia often, though not always, recede with continued pharmacotherapy beyond acute treatment. Despite symptomatic overlap of dysthymia with chronic fatigue syndrome - especially with respect to the cluster of symptoms consisting of low drive, lethargy, lassitude and poor concentration - neither the psychopathologic status, nor the pharmacologic response profile of the latter syndrome is presently understood. Chronic fatigue today is where dysthymia was two decades ago. We submit that the basic science - clinical paradigm that has proven so successful in dysthymia could, before too long, crack down the conundrum of chronic fatigue as well. At a more practical level, we raise the possibility that a subgroup within the chronic fatigue group represents a variant of dysthymia.

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BACKGROUND: The purpose of this study was to evaluate the reliability and psychometric properties of the Semistructured Affective Temperament Interview, and determine cut-offs for each temperament. METHOD: 1010 Italian students aged between 14 and 26 were evaluated by means of the Akiskal and Mallya criteria in a Semistructured Interview for depressive, cyclothymic, hyperthymic, and irritable temperaments. RESULTS: This instrument has very good reliability and internal consistency. The percentage of subjects with a z-score higher than the second positive standard deviation ( + 2 SD) on the scales of depressive and cyclothymic temperaments are 3.6% and 6.3% (reaching scores of 7/7 and 9/10), respectively. Hyperthymic traits, on the other hand, are widespread in our sample: most subjects are included within the second positive standard deviation ( + 2 SD), and 8.2% of these reach a 7/7 score; therefore, the problem of defining a cut-off for this temperament is still open. By contrast, the irritable temperament is rare, conforming to a non-gaussian distribution, with 2.2% of cases above the second positive standard deviation ( + 2 SD). LIMITATION: The data are based on subject report without collateral information and external validation. CONCLUSION: This study contributes to more accurate definition of cut-offs for individual temperament scales. The standardization of the interview thus makes it possible to compare three out of four temperamental scales, showing the dominant temperamental characteristics for each subject. Prospective studies are needed to demonstrate the stability of these traits over time.

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OBJECTIVE: It is generally accepted that temperament is not entirely stable, and that it changes with development, particularly in juvenile subjects; also, some temperaments are believed to be inherently more unstable. There is a great deal of current interest in Kraepelin's thesis that temperamental dysregulation in juvenile subjects represents the constitutional foundation from which the more florid episodes of manic-depressive illness arise; the cyclothymic, hyperthymic, depressive and irritable temperaments under consideration might represent the first observable phenotypes of the genetic diathesis for bipolarity. The analyses on the temperamental attributes in juvenile subjects were undertaken within this theoretical framework. METHOD: We evaluated 206 Italian high school students (14-18 years old) by means of a semi-structured affective temperament interview (TEMPS-I) at T0 and T1 two years later. Age, sex and psychometric properties of TEMPS-I raw scale score and weighted cut-off (as specially weighted linear combination of items) were used as predictive variables of stability. RESULTS: Affective temperaments had a low to moderate level of stability, reaching 60% in the case of subjects with dominant cyclothymic temperament. The stability of the depressive temperament was primarily related to its weighted cut-off. The stability of the hyperthymic temperament appeared related to male sex, young age, and total scale score. Male sex represented the best stability predictor for the cyclothymic temperament as well. The group of subjects with an unstable depressive temperament showed a change toward the dominant cyclothymic temperament, whereas individuals with unstable hyperthymic temperamental traits moved on towards the dominant cyclothymic and depressive temperaments. The irritable construct was the least stable. LIMITATIONS: The infeasibility of a multiwave design represents the main limitation in evaluating the predictors of stability. Furthermore, in the present analyses, the size of the cyclothymic subsample was small. CONCLUSION: Our data indicate considerable fluctuation and instability in depressive and hyperthymic temperaments in mid-adolescence. The cyclothymic temperament appears to be the most stable. Interestingly, cyclothymic moodiness appears more persistent in juvenile males; likewise persistent hyperthymic traits appear more of a "male" attribute. CLINICAL AND PUBLIC HEALTH IMPLICATIONS: We submit that these sex-relevant traits could be important in the risk of developing juvenile bipolarity. Literature review indicates that clinical studies, albeit on small samples, have already provided some support for this thesis. Larger studies on epidemiological samples could be more informative from a public health perspective. A user-friendly affective temperament questionnaire, which is under development, is critical for the methodology of such studies. Our study indicates that the present version of the Akiskal-Malya questionnaire can be easily used post-pubertally. Age adjustment must be considered for younger subjects.

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A role of psychic stress in precipitating hyperthyroid Graves' disease has been suggested, but the evidence in support of this pathogenetic mechanism is conflicting. In this study we investigated the possible occurrence of Graves' disease in patients with panic disorder, a psychiatric condition characterized by recurrent endogenous stress. The study group included 87 consecutive patients suffering from panic disorder since 1 to 30 years: 17 males (mean age 31.3, range 26-43 years) and 70 females (mean age 37.6, range 15-73 years). Two hundred and sixty-two normal subjects with no present or past history of psychiatric disorder served as controls. Patients were submitted to a full evaluation of the thyroid that included physical examination, assays for free thyroid hormones, TSH, thyroglobulin (TgAb), thyroperoxidase (TPOAb) and TSH receptor (TRAb) antibodies, and thyroid echography. The prevalence of circulating TgAb and/or TPOAb in patients with panic disorder did not differ from that in the control group. Twelve patients with panic disorder (13.7%) had circulating TgAb and/or TPOAb, but none had TRAb. Three out of 12 patients with thyroid antibodies, indicating a genetic susceptibility to autoimmune thyroid disease, had a family history of clinical thyroid autoimmunity, and 4 of them had a hypoechogenic pattern of the thyroid at ultrasound suggesting autoimmune thyroiditis. None of the patients with panic disorder had a previous history of hyperthyroidism. On examination, clinical hyperthyroidism or endocrine ophthalmopathy were not found in any of them. A small goiter was appreciated by palpation in 16 patients (18.3%). Free thyroid hormones and TSH were within the normal range in all patients but one: a 55-year old lady with normal serum free thyroid hormones and undetectable TSH. During an 18-month follow-up she did not develop hyperthyroidism and her TSH spontaneously returned in the normal range. Considering the individual duration of panic disorder, evidence for previous or present Graves' hyperthyroidism was not found for a total of 478 patient-years of exposure to recurrent endogenous stress in the whole study group, and for a total of 39 patient-years in patients with a genetic susceptibility to autoimmune thyroid disease. In conclusion, we found that recurrent endogenous stress did not precipitate Graves' hyperthyroidism in a series of 87 patients with panic disorder, encompassing a total of 478 patient-years of exposure to stress. Failure to activate the hypothalamic-pituitary-adrenal axis by endogenous stress due to panic disorder as opposed to exogenous stress due to life-events might explain why panic disorder does not precipitate Graves' hyperthyroidism.

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BACKGROUND: Although most personality constructs have been standardized in population studies, cyclothymic, depressive, irritable and hyperthymic temperaments putatively linked to mood disorders have been classically derived from clinical observations. METHODS: We therefore administered the semi-structured affective temperament schedule of Memphis, Pisa, Paris and San Diego, Interview version (TEMPS-I) -- in its original University of Tennessee operationalization -- to 1010 Italian students aged between 14 and 26. The interview, administered in a randomized format, took 20 min per subject. RESULTS: The semi-structured interview was easy to administer and well accepted by subjects, with no refusals. Principal component analysis with varimax rotation confirmed the hypothesized four-dimensional factor structure of the interview, with good to excellent internal consistency. Furthermore, discriminant analysis and multiple regression provided suggestions for identifying the traits that are most useful in defining a weighted cut-off for each of the temperaments (and which, with minor exceptions, are in agreement with those previously proposed on clinical grounds). In an additional exploratory factorial analysis, a depressive type which loads negatively on hyperthymia was distinguished from cyclothymia; the irritable temperament did not appear to have significant loading on either factor. LIMITATION: All the present analyses were internal to the scale itself, but ongoing studies are comparing them with other systems of temperament as well as testing their clinical cogency for affectively ill populations. CONCLUSION: While more work needs to be done on better operationalization of the irritable temperament, our findings overall support the existence -- in a relatively young nonpatient population -- of cyclothymic, depressive and hyperthymic types according to the classic descriptions of Kraepelin, Kretschmer and Schneider, in their TEMPS-I operationalization. CLINICAL IMPLICATIONS: Coupled with a previous report identifying 10% of the same 14-26-year-old nonpatient population meeting an empirically defined statistical cut-off for these temperaments, the present data define the putative 'fundamental states' that Kraepelin considered to be the personal predisposing anlagé of major affective disorders.

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A group of 33 sportsmen and 43 sportswomen and a group of 488 subjects (less than 30 years old) selected from a sample of 816 subjects representative of the general Italian population were compared using the factor scores and total scores on the Italian version of the Buss and Durkee questionnaire. Analysis suggests a positive correlation between aggressiveness and sport and are compatible with the hypothesis that sporting activities serve as a means of controlling aggressiveness of women and help the individual psychosocial development of men. The decision to practice sports would seem to be connected with the needs to conform to cultural stereotypes, which portray the man as aggressive and the women as gentle and submissive.

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We studied 259 female inpatients with bipolar spectrum disorders, of whom 26 (10%) were schizoaffective. Of the remaining 233, 61 (27%) met our conservatively set criteria for index mixed episodes (simultaneous presence of depressive and manic syndromes). These patients with rigorously defined mixed states were, in turn, about equally divided between psychotic and non-psychotic subgroups. The psychotic mixed patients (n = 32) were closer to the bipolar I pattern, and more often seem to come from a familial background of psychotic mood disorders; the nonpsychotic mixed patients (n = 29) conformed more closely to the bipolar II pattern, and more often had a hyperthymic and cyclothymic temperament and a family background of non-psychotic disorders and substance abuse. A three-way comparison between psychotic manic (n = 24), psychotic mixed (n = 32), and schizoaffective (n = 26) patients revealed few significant differences in temperamental, familial and course patterns. As expected, psychotic manic patients more often arose from a hyperthymic base and pursued a predominantly manic course; psychotic mixed patients were less likely to arise from such a base and more likely to pursue a mixed course. Finally, schizoaffective had earlier age at onset and longer duration of illness, suggesting that these patients had a more severe illness. Otherwise, interepisodic social adaptation was comparable in the three psychotic groups. The findings overall suggest that the presence of psychosis had relatively little impact on mixed states, which appear more based on temperamental characteristics.

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Data on 108 hospitalized bipolar I women were analyzed to characterize those whose course was marked with at least one mixed episode (i.e. an episode with concomitant manic and depressed features) on the basis of various anamnestic and cross-sectional clinical features in comparison with those without mixed episodes. Our data revealed a later age of appearance of the first mixed episode in the course of bipolar illness with a tendency to recur true to type; greater prevalence of mood incongruent psychotic features; lower frequency of hyperthymic temperament; and familial depressive, rather than bipolar, disorders. These characteristics tend to identify the mixed state as a distinct longitudinal pattern of manic-depressive illness.

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The problem of whether rapid-cycling (RC) bipolar disorder is more frequently associated than non-rapid-cycling (NRC) bipolar disorders with thyroid dysfunction was investigated in two groups of 11 women matched for age and therapy. Seven patients in each group were under chronic lithium therapy. Both RC and NRC patients, as compared to euthyroid controls, showed a reduction in mean total and free thyroid hormone concentrations, subnormal values of free thyroxine being found in four RC and three NRC patients. No patient had supranormal baseline thyroid stimulating hormone (TSH) values, but an exaggerated TSH response to thyrotropin releasing hormone was found in three RC and two NRC patients: all these patients had been receiving lithium therapy for more than one year. No differences in the prevalence of goiter and thyroid-directed autoantibodies were observed in the two groups. These data confirm that bipolar disorder, especially during treatment with lithium, is associated with at least subclinical hypothyroidism, and suggest that RC patients do not differ from NRC patients in the prevalence of spontaneous or lithium-induced thyroid hypofunction. Lithium-induced hypothyroidism is likely to be related to the length of treatment.

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TSH secretion, with particular regard to the nocturnal surge of the hormone, was evaluated in 15 women (age range, 35-66 yr; mean, 50 yr) with untreated major endogenous depression and 15 healthy women (age range, 32-67 yr; mean, 53 yr) using an ultrasensitive assay. Mean morning (0830 h) TSH values did not differ in the 2 groups (1.3 +/- 02 mU/L in depressives and 1.4 +/- 0.1 mU/L in controls), whereas mean nighttime (2400-0200 h) values were significantly reduced in depressives (1.5 +/- 0.3 vs. 3.1 +/- 0.3 mU/L; P less than 0.0005). At variance with the control group, morning and nighttime TSH values did not differ in the depressives. The nocturnal serum TSH surge was abolished in 14 of 15 depressed patients. The mean peak TSH value after TRH was slightly yet significantly lower in the depressives. Patients with subnormal (less than 0.4 mU/L) TSH values in the morning had a serum TSH increase after TRH less than 2 mU/L in 5 of 6 cases and a lack of the nocturnal TSH surge in 6 of 6. Among the 9 patients with normal TSH values in the morning, the nocturnal serum TSH surge was lost in 8 of 9, whereas the response to TRH was normal in all. The depressives, at variance with other reports, showed significantly lower values of total and free thyroid hormones. Mean serum sex hormone-binding globulin (SHBG) and ferritin were also significantly reduced. In conclusion, major endogenous depression is associated with a major impairment of TSH secretion, which baseline TSH measurements in the morning and the evaluation of the TSH response to TRH may not reveal. In this regard, the loss of the nocturnal serum TSH rise would appear to be a more sensitive indicator of hypothalamus-pituitary-thyroid axis alterations in depressives than the TRH test, which is commonly used in the evaluation of these patients. The lack of the nocturnal TSH surge may be responsible for the reduced thyroid hormone secretion and supports the case for some degree of central hypothyroidism in endogenous depression.

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We compared 3H-imipramine binding in 10 major depressives with that in 29 healthy volunteers, 13 patients with panic disorder, 9 patients with bulimia, 9 suicide attempters, and 6 schizophrenic patients. None of the comparison groups had histories of major mood disorders, except the suicide attempters. We found a significant reduction of the maximum binding capacity (Bmax) in all groups of patients as compared with healthy controls. These data cast doubt upon the specificity of the decrease of platelet 3H-imipramine binding in major depression, but suggest a possible pharmacological common denominator involving the serotonin system.

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The distribution of pinazepam and its metabolite N-desmethyldiazepam was studied in fetuses of New Zealand rabbits on the 20th and 27th day of pregnancy. The concentrations of both compounds were also measured in the maternal brain, liver and uterus. Pregnant rabbits were sacrificed at 0.5, 2, 4 and 12 h after intravenous administration of pinazepam (5 mg/kg). The concentrations of pinazepam and N-desmethyldiazepam in various biological specimens were measured by a specific gas-chromatographic procedure. Pinazepam and N-desmethyldiazepam rapidly crossed the placenta. In 20 day old fetuses, comparable concentrations of pinazepam were found in the liver, brain, heart, lungs and kidneys. In contrast, the liver of 27 day old fetuses accumulated pinazepam at concentrations higher than the other tissues. The hepatic extraction of pinazepam, already described in adult rabbits (1), develops prenatally. A preferential accumulation of pinazepam rather than N-desmethyldiazepam was also observed in the maternal uterus. In this tissue the concentrations of pinazepam were 5-10 times higher on the 27th rather than the 20th day of pregnancy. The stage of pregnancy influences the distribution pattern of pinazepam in rabbit fetuses and their mothers.

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