Factor structure and reliability of the Italian adaptation of the Hypomania Check List-32, second revision (HCL-32-R2).

OBJECTIVE: To assess the psychometric properties of the Italian adaptation of the Hypomania-Check-List 32-item, second revision (HCL-32-R2) for the detection of bipolarity in major depressive disorder (MDD) treatment-seeking outpatients. METHODS: A back-to-back Italian adaption of the "Bipolar Disorders: Improving Diagnosis, Guidance, and Education" English module of the HCL-32-R2 was administered between March 2013 and October 2014 across twelve collaborating sites in Italy. Diagnostic and Statistical Manual Fourth edition (DSM-IV) diagnoses were made adopting the mini-international neuropsychiatric interview, using bipolar disorder (BD) patients as controls. RESULTS: In our sample (n=441, of whom, BD-I=68; BD-II=117; MDD=256), using a cut-off of 14 allowed the HCL-32-R2 to discriminate DSM-IV-defined MDD patients between "true unipolar" (HCL-32-R2(-)) and "sub-threshold bipolar depression" (HCL-32-R2(+)) with sensitivity=89% and specificity=79%. Area under the curve was .888; positive and negative predictive values were 75.34% and 90.99% respectively. Owing to clinical interpretability considerations and consistency with previous adaptations of the HCL-32, a two-factor solution (F1="hyperactive/elated" vs. F2="irritable/distractible/impulsive") was preferred using exploratory and confirmatory factor analyses, whereas items n.33 ("I gamble more") and n.34 ("I eat more") introduced in the R2 version of the scale slightly loaded onto F2 and F1 respectively. Cronbach׳s α=.88 for F1 and .71 for F2. LIMITATIONS: No cross-validation with any additional validated screening tool; treatment-seeking outpatient sample; recall bias; no systematic evaluation of eventual medical/psychiatric comorbidities, current/lifetime pharmacological history, neither record of severity of current MDE. CONCLUSIONS: Our results seem to indicate fair accuracy of HCL-32 as a screening instrument for BD, though replication studies are warranted.

Personality and dementia.

Personality describes persistent human behavioral responses to broad classes of environmental stimuli. Change in personality may be an early sign of dementia. Our goal was to review scientific literature on the association between personality and dementia. Medline and Google Scholar searches were conducted for relevant articles, chapters, and books published since 1980. Search terms used included personality, dementia, Alzheimer's disease, frontotemporal dementia, dementia with Lewy bodies. People with dementia commonly exhibit changes in personality that sometimes precede the other early clinical manifestations of the condition, such as cognitive impairment. Premorbid personality might be a determining factor so that caricature or exaggeration of original personality emerges as dementia progresses. Although it is generally accepted that these personality changes reflect the impact of progressive brain damage, there are several possible patterns of personality alterations with dementia. Early identification of personality modifications might assist with the timely diagnosis of dementia.

Treatment adherence towards prescribed medications in bipolar-II acute depressed patients: relationship with cyclothymic temperament and "therapeutic sensation seeking" in response towards subjective intolerance to pain.

BACKGROUND: Treatment adherence (TA) is crucial during almost any phase of bipolar disorder (BD), including type-II (BD-II) acute depression. While a number of issues have been traditionally accounted on the matter, additional factors should be likewise involved, including affective temperaments and some clinically suggestive psychopathological traits whose systematic assessment represents the aim of this study. METHODS: Two hundred and twenty BD-II acute depressed outpatients were consecutively evaluated using the Structured Clinical Interviews for Diagnostic and Statistical Manual for Mental Disorders-Fourth Edition Axis-I and II Disorders, Hamilton scales for Depression and Anxiety, Temperament Evaluation of the Memphis Pisa Paris San Diego-Auto-questionnaire-110-item, Visual Analogue Scale (VAS), Zuckerman's Sensation-Seeking Scale-Form-V (SSS-V), Barratt's Impulsivity Scale-11-item, State-Trait Anxiety Inventory modules, Severity module of the Clinical Global Impression Scale for BD, Morisky 8-Item Medication Adherence Scale (MMAS-8) and the Clinician Rating Scale (CRS). Patients were divided into non-adherent vs. treatment-adherent cases depending on MMAS-8+CRS scores. RESULTS: In the TA(-) group, higher VAS and cyclothymic temperament scores were highly correlated (r=.699; p≤.001). Those latter scores, along with SSS-V scores and the occurrence of lifetime addiction to painkiller and/or homeopathic medications available over the counter defined a "therapeutic sensation seeking" pattern allowing to correctly classify as much as 93.9% [Exp(B)=3.490; p≤.001] of TA(-) cases (49/220). LIMITS: Lack of objective TA measures and systematic pharmacological record; recall bias on some diagnoses; and relatively small sample size. CONCLUSIONS: Stating the burden of TA in BD, additional studies on this regard are aimed, ideally contributing to enhance the management of BD itself.

Sensation seeking in major depressive patients: relationship to sub-threshold bipolarity and cyclothymic temperament.

BACKGROUND: High levels of sensation seeking (SS) have been traditionally reported for lifetime bipolar disorder (BD) and/or substance use disorder (SUD) rather than major depressive disorder (MDD). Nonetheless, a renewed clinical attention toward the burden of sub-threshold bipolarity in MDD, solicits for a better assessment of "unipolar" major depressive episodes (MDEs) via characterization of putative differential psychopathological patterns, including SS and predominant affective temperament. METHODS: Two hundred and eighty currently depressed cases of MDD and 87 healthy controls were screened using the Zuckerman's sensation seeking scale-Form-V, the Hypomania Check List-32-item (HCL-32), the Temperament Evaluation of Memphis, Pisa, Paris and San Diego Auto-questionnaire-110-item, the Barratt Impulsivity Scale-11-item, the State-Trait Anxiety Inventory modules and the Structured Clinical Interview for DSM-IV axis-I disorders. Cases were divided into HCL-32(+)(sub-threshold bipolar)/HCL-32(-)("true" unipolar depressed) depending on the HCL-32 total score. RESULTS: Upon correlation and multivariate regression analyses, the HCL-32(+) patients showed the highest levels of SS, higher prevalence of cyclothymic temperament, and higher rates of multiple lifetime axis-I co-morbidities, including SUD. LIMITS: Recall bias on some diagnoses, including BD, grossly matched healthy control group, lack of ad-hoc validated measures for ADHD, SUD, or axis-II disorders. CONCLUSIONS: In our sample, the occurrence of higher levels of SS in "sub-threshold" bipolar cases outlined a differential psychopathological profile compared to DSM-defined "true unipolar" cases of MDE. If confirmed by replication studies, these findings may aid clinicians in delivering a more accurate diagnosis and a safer use of antidepressants in some MDD cases.

Depressive symptoms in Parkinson's disease.

OBJECTIVE: We aimed to investigate the relationship between the presence and severity of depression and the degree of motor and functional disability in Parkinson's disease (PD). METHODS: One hundred twenty-two outpatients with PD were enrolled in a neurology department: 65 satisfied the Diagnostic and Statistical Manual of Mental Disorder, Fourth Edition criteria for major depression, and 57 did not (PD-C). Depressive symptoms were assessed by means of the Hamilton Rating Scale for Depression (HRSD), and the PD severity was assessed according to the Hoehn and Yahr System. Activities of daily living and motor symptoms were measured by the Unified PD Rating Scale (UPDRS), parts II and III. RESULTS: Twenty-nine patients had a mild depression (HRSD total score ranging between 8 and 17), 30 had a moderate depression (HRSD total score ranging between 18 and 24), and 6 had a severe depression (HRSD total score, ≥25). By comparing the 3 groups of patients, it emerged that those with a severe depression showed significantly higher scores at the UPDRS II, UPDRS III, and HY scales than did PD-C or patients with a mild depression. Moreover, patients with a moderate depression scored significantly higher on the UPDRS II, UPDRS III, and HY scales than did PD-C or those with a mild depression. CONCLUSIONS: Our findings suggest that depression and motor symptoms/well-being are highly intertwined in patients with PD.

Longitudinal follow-up of bipolar disorder in women with premenstrual exacerbation: findings from STEP-BD.

OBJECTIVE: The impact of hormonal fluctuation during the menstrual cycle on the course of bipolar disorder is poorly understood. The authors determined the course of illness and time to relapse of bipolar disorder in prospectively followed women with premenstrual exacerbation. METHOD: Participants were 293 premenopause-age women with bipolar disorder who were followed prospectively for 1 year as part of the Systematic Treatment Enhancement Program for Bipolar Disorder. Frequency of mood episodes was compared between 191 women with premenstrual exacerbation (65.2%) and 102 women without. Among 129 women who were in recovered status at baseline, time to relapse was compared between 66 women with premenstrual exacerbation (51.2%) and 63 without. RESULTS: During follow-up, the group with premenstrual exacerbation had more episodes (primarily depressive) than did the group without, but they were not more likely to meet criteria for rapid cycling during this period. In contrast, they were more likely to report rapid cycling retrospectively. Women with premenstrual exacerbation had a shorter time to relapse and were at greater risk for relapse, but this association was not significant after adjustment for retrospectively reported rapid cycling. Women with premenstrual exacerbation had more depressive and mood elevation symptoms overall. CONCLUSIONS: Women with bipolar disorder and premenstrual exacerbation have a worse course of illness, a shorter time to relapse, and greater symptom severity, but they are not more likely to meet criteria for rapid cycling. Premenstrual exacerbation may be a clinical marker predicting a more symptomatic and relapse-prone phenotype in reproductive-age women with bipolar disorder.

Associations between brain-derived neurotrophic factor plasma levels and severity of the illness, recurrence and symptoms in depressed patients.

BACKGROUND: There is increasing evidence that the brain-derived neurotrophic factor (BDNF) is involved in the pathophysiology of mood disorders and that its peripheral levels represent a reliable mirror of its concentration in the brain. The aim of the present study was to measure BDNF plasma levels in patients affected by major depression and to explore the possible relationship between the biological parameter and characteristics of the illness. METHOD: BDNF plasma levels were evaluated in 30 inpatients suffering from major depression, according to DSM-IV criteria, by means of a commonly employed ELISA method. The clinical characteristics were assessed by the Hamilton Rating Scale for Depression (HRSD) and the Clinical Global Impression Scale. RESULTS: BDNF plasma levels were significantly lower in the patients with the severest illness compared with the others, and the same was true for patients with dissociative symptoms, severe sleep disturbance and recurrent depression. A significant and negative correlation was observed between the biological parameter and the retardation factor score of the HRSD. CONCLUSION: These findings suggest that low BDNF levels are related to both recurrence and severity of depression, as well as to symptoms typical of dysfunctions of the hypothalamic-pituitary-adrenal axis.

Brain-derived neurotrophic factor plasma levels in patients suffering from post-traumatic stress disorder.

In both animals and humans, stress has been demonstrated to reduce the expression of the Brain-Derived Neurotrophic Factor (BDNF), a neurotrophin (NT) which promotes the proliferation, survival and differentiation of neurons. Although traumatic events have been found to be associated with lower BDNF plasma levels in affective disorders, no study has explored this parameter in patients with post-traumatic stress disorder (PTSD). We, therefore, measured BDNF plasma level in 18 patients with PTSD and in 18 healthy control subjects. Diagnoses were assessed by the Structured Clinical Interview for DSM-IV, while the specific symptoms were examined in the patients by means of the Impact of Event Scale for PTSD and the traumas experienced were assessed by using the Life Events Checklist. BDNF plasma levels were evaluated by means of a standardized Elisa method. The results, while showing significantly lower BDNF levels in PTSD patients, as compared with those of healthy subjects (p=0.001), although obtained in a small sample size, would suggest that this NT may be involved in the pathophysiology of PTSD.

Plasma Brain-Derived Neurotrophic Factor in treatment-resistant depressed patients receiving electroconvulsive therapy.

There is an increasing evidence that the Brain-Derived Neurotrophic Factor (BDNF) could be involved in the mode of action of antidepressants and, perhaps, of ECT. This study aimed to investigate whether the clinical course of medication-resistant depressed patients following a course of ECT might be associated with changes of plasma BDNF concentrations. Our findings showed that at T0 (baseline) plasma BDNF levels of patients were significantly lower than those of control subjects, and that at T2 (after ECT) were significantly increased in parallel with the decrease of the Hamilton Rating Scale for Depression (HRSD) total score. However, only remitter patients who showed higher baseline BDNF levels than non-remitters reached normalized BDNF levels after ECT. These findings would suggest the potential usefulness of baseline plasma BDNF levels as predictors of response to ECT in treatment-resistant depressed patients.

Diurnal variation of plasma brain-derived neurotrophic factor (BDNF) in humans: an analysis of sex differences.

Scant information is available on the diurnal variation of peripheral neurotrophic factors, including brain-derived neurotrophic factor (BDNF), in human beings. We explored plasma and serum BDNF levels at three different clock times in a study of 28 healthy subjects of both sexes. Statistically significant diurnal variation in plasma BDNF level was detected in men, with the peak at 08:00 h and nadir at 22:00 h. At this time, the plasma BDNF concentration of men was significantly lower than that of women (p=.02). However, no diurnal variation was found either in plasma BDNF of women, in either the follicular or luteal phases of the menstrual cycle, or in serum BDNF level in both men and women. These findings support the concept of rhythmic variation in plasma BDNF regulation that seems to be sex-related.

BDNF level in the rat prefrontal cortex increases following chronic but not acute treatment with duloxetine, a dual acting inhibitor of noradrenaline and serotonin re-uptake.

AIMS: Brain-Derived Neurotrophic Factor (BDNF) has a central role in neuronal survival, differentiation, and plasticity. The brain level of BDNF is changed by several mood stabilizers and antidepressant drugs acting on neurotransmitters such as noradrenaline and serotonin. We investigated the effects of acute and chronic treatment with Duloxetine, a new drug blocking the re-uptake of serotonin and noradrenaline (SNRI), on BDNF level in the prefrontal cortex, cerebrospinal fluid, plasma, and serum. METHODS: Wistar male rats were treated with acute (single treatment) and chronic oral administration (14 days) of different concentrations of Duloxetine (10, 30, and 100 mg/kg/day). At the end of the treatment periods, samples of blood, CSF and the prefrontal cortex were collected. BDNF levels were measured by ELISA. Levels of mature and precursor form of BDNF were measured by Western blot analysis. RESULTS: Animals treated with the Duloxetine at all concentrations and examined after 1 and 24 h (single treatment) did not reveal a significant change in the total BDNF level. In animals treated for 14 days with Duloxetine at 30 and 100 mg/kg, the total BDNF level increased significantly in the prefrontal cortex and CSF, but not in the plasma and serum. Using a specific antibody and Western blot we showed that the mature, but not the precursor, form of BDNF was significantly increased in the prefrontal cortex of rats treated for 14 days with Duloxetine at 30 mg/kg/day. CONCLUSIONS: Our results show a major finding that repeated, but not single, Duloxetine treatment increases the level of BDNF in the prefrontal cortex.

Plasma and serum brain-derived neurotrophic factor (BDNF) in depressed patients during 1 year of antidepressant treatments.

BACKGROUND: Brain-derived neurotrophic factor (BDNF) has been hypothesized to be involved in the neurobiology of major depression. The aim of this study was to assess the possible relationships between depressive symptoms and serum and/or plasma BDNF levels during 1 year of antidepressant treatment. METHODS: Plasma and serum BDNF levels were assayed in 15 drug-free depressed patients and in 15 healthy control subjects at baseline and the 1st, 3rd, 6th and 12th month of antidepressant treatment. RESULTS: At baseline, patients' serum and plasma BDNF levels were significantly lower (p<.001 and p=.004, respectively) than those found in healthy control subjects. However, while from the 1st month of treatment patients' plasma BDNF levels did not differ significantly from those observed in healthy control subjects, serum BDNF levels in patients remained significantly lower at all times. LIMITATIONS: The main limitations of the current study are represented by the small sample size and the high discontinuation rate. CONCLUSIONS: Untreated depressed patients showed reduced baseline serum and plasma BDNF levels, as compared with control subjects. The clinical improvement paralleled the normalization of plasma BDNF after 1 month of treatment, while, at every assessment time, patients' serum BDNF levels were lower than those of control subjects. This would suggest that serum BDNF might represent a non-specific trait marker of depression.

Romantic attachment in patients with mood and anxiety disorders.

INTRODUCTION: Romantic attachment is the establishment of a relationship with a partner and is strongly influenced by the individual's attachment style. While several studies have shown that attachment style may contribute to the development of psychopathology, less information is available for romantic attachment. The aim of the present study was to compare romantic attachment styles among patients with different mood and anxiety disorders and control subjects. METHOD: The study sample included a total of 126 outpatients, 62 of whom were affected by bipolar disorders, 22 by major depressive disorder (MDD), 27 by panic disorder, 15 by obsessive-compulsive disorder, and 126 healthy control subjects. Romantic attachment was assessed by means of the Italian version of the "Experiences in Close Relationships" (ECR) questionnaire. RESULTS: The results showed that the secure attachment style was more frequent in the control group, while the preoccupied style prevailed among the patients, with no difference among the diagnostic categories. The scores of the ECR anxiety and avoidance scales were significantly higher in the patients than in the control subjects. A trend toward higher ECR anxiety scale scores in women with panic disorder was detected, with the opposite being true for MDD. CONCLUSION: Our findings indicate that patients with different psychiatric disorders would be characterized by higher scores on both the ECR anxiety and the avoidance scales, as well as by the preoccupied style of attachment. In addition, women with panic disorder and MDD seem to be characterized by, respectively, higher and lower scores of the ECR anxiety scale than men.

Health-related quality of life and functioning in remitted bipolar I outpatients.

The aim of this study was to characterize the health-related quality of life (HR-QOL) and functioning in 90 bipolar I remitted outpatients. According to Diagnostic and Statistical Manual of Mental Disorders IV remission specifiers, patients were categorized into 4 groups: group 1, fully remitted; group 2, less than 2 months remitted; group 3, with persisting manic symptoms; group 4, with persisting depressive symptoms. The severity of psychopathology was evaluated by using the Bech-Rafaelsen Mania-Melancholia Scale. The HR-QOL, functioning, and insight were assessed via the medical outcomes study 36-item short form, the global assessment of functioning scale, and the scale to assess unawareness of mental disorder, respectively. Fully remitted patients reported the highest scores in almost all domains of medical outcomes study 36-item short form, and had significantly higher scores on physical functioning, general health, social functioning, and mental health compared to patients with persisting depressive symptoms. Furthermore, patients with persisting manic symptoms reported significantly higher scores on general health, vitality and mental health than the group with persisting depressive symptoms. In contrast, the global assessment of functioning scale score differed among the 4 groups, with fully remitted patients reporting higher, although not statistically significant, scores than the other groups. Our data suggest that the persistence of depressive or manic symptoms seem to affect self-report measures of HR-QOL. An affectively biased cognition may explain the gap between patient's perception of functioning and estimated functional adjustment, as assessed by clinicians.

Subthreshold mania as predictor of depression during interferon treatment in HCV+ patients without current or lifetime psychiatric disorders.

BACKGROUND: Depression is considered the most frequent interferon (IFN)-alpha-induced psychiatric disorder. However, other neuropsychiatric side effects of IFN treatment, such as irritability, anxiety, and manic episodes, are reported as well. We analyzed the impact of lifetime manic-hypomanic symptoms and anxiety on the development of depression in hepatitis-C-virus-infected subjects treated with two different types of IFN-alpha. METHODS: At baseline, subjects received thorough diagnostic assessment to exclude lifetime or current psychiatric symptoms. During treatment, subjects were administered interviewer-based and self-report instruments. RESULTS: Six (12%) of 49 individuals with a negative history of psychiatric disorders developed major depression during treatment with IFN. The onset of depression was significantly associated with the presence of lifetime subthreshold manic-hypomanic symptoms. Subjects exceeding manic threshold were more likely to develop depression than those below threshold (33.3% vs. 7.5%, P=.033). CONCLUSIONS: Our data suggest that individuals treated with IFN with no past history of psychiatric disorders are more likely to develop depression if they experienced subthreshold manic-hypomanic symptoms in their lifetime. These findings derive from an exploratory study and may have important implications for the prevention of IFN-induced depression if replicated in larger studies.

A relationship between oxytocin and anxiety of romantic attachment.

The formation of social bonding is fundamental for several animals, including humans, for its relevant and obvious impact upon reproduction and, thus, survival of the species. Recent data would suggest that oxytocin might be one of the mediators of this process. Given the paucity of data on the possible involvement of oxytocin in human attachment, the present study was aimed to explore the possible relationships between the plasma levels of this neuropeptide and romantic attachment in healthy subjects. Forty-five healthy subjects who volunteered for the study, were included in the study. The romantic attachment was assessed using the Italian version of the so-called "Experiences in Close Relationships" (ECR), a self-report questionnaire for measuring this parameter in adults. The results showed that attachment anxiety and oxytocin are positively linked in romantic attachment to a statistically significant degree (r = 0.30, p = 0.04), that is, the higher the oxytocin levels the higher the score on the anxiety scale of the ECR. The authors suggest the hypothesis that this link represents one of the biological processes resulting in those rewarding emotions related to romantic attachment.

Clinical significance of lifetime mood and panic-agoraphobic spectrum symptoms on quality of life of patients with rheumatoid arthritis.

BACKGROUND: Previous studies suggested that rheumatoid arthritis (RA) is associated with depressive and anxiety symptomatology. The well-being and functioning of patients with RA may be significantly influenced by subthreshold psychiatric comorbidity. Health-related quality of life (HRQoL) of patients with RA, compared with the Italian norms and patients with diabetes, was assessed by the influence of lifetime mood and panic-agoraphobic spectrum symptoms and demographic and clinical variables. METHODS: Ninety-two patients were consecutively recruited at the Department of Rheumatology at the University Hospital of Pisa, Italy. All patients met diagnostic criteria of RA according to the American College of Rheumatology. Health-related quality of life was measured using the Medical Outcomes Study 36-Item Short-Form Health Survey questionnaire (MOS SF-36). Mood and panic-agoraphobic spectra were assessed by two different structured self-report instruments: the Mood Spectrum (MOODS-SR) and the Panic-Agoraphobic Spectrum (PAS-SR), respectively. RESULTS: Patients with RA were compared, as regards the MOS SF-36 scale scores, with the Italian normative population and patients with diabetes. Compared with the Italian population, patients with RA showed significantly lower MOS SF-36 scale scores, except for role emotional. Moreover, patients with RA scored significantly lower on the role physical, bodily pain, and social functioning scales compared with patients with diabetes and higher on role emotional and mental health. A significant worsening of all MOS SF-36 scale scores was related to higher scores of the depressive domains of MOODS-SR, except for social functioning and bodily pain. A statistically significant negative association was also found between PAS-SR total score and the MOS SF-36 scales physical functioning, vitality, role emotional, and mental health. There were no statistically significant correlations between MOS SF-36 scales and the manic MOODS spectrum. In the multivariate models, the negative correlations between depressive MOODS, role emotional, and mental health were confirmed and the severity of arthritis showed a significant impact on all MOS SF-36 areas with the exception for social functioning; moreover, manic MOODS was associated with better general health. CONCLUSIONS: The present report shows that lifetime depressive spectrum symptoms negatively affects HRQoL of patients with RA and subthreshold mania improves the perception of general health. Diagnosis and appropriate clinical management of depression, including subthreshold symptoms, might enhance HRQoL in these patients.