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(2003). Hormone replacement therapy in climacteric and aging brain. Climacteric: Vol. 6, No. 3, pp. 188-203.

Using a structured interview, the Personality Disorder Examination, the authors examined DSM-III-R personality disorders in 37 patients with generalized anxiety disorder (GAD), 40 with panic disorder (PD), and 38 with recurrent major depressive disorder (RD) in order to delineate personality disorders associated with these Axis I diagnoses. A higher proportion of PD than GAD and RD patients met criteria for one or more personality diagnosis (50% vs. 41% and 34%, respectively), and PD patients had a greater variety of personality disorders

Although the role of anxiety disorders on the development of Post-partum Depression (PPD) have already been studied in literature, that of individual anxiety disorders has not received specific attention. The aim of this study is to investigate the role of Panic Disorder (PD) and family history for PD as risk factors for PPD.Six hundred women were recruited in a prospective, observational study at the 3rd month of pregnancy and followed up until the 6th month after delivery. At baseline, risk factors for PPD, Axis-I disorders and family history for psychiatric disorders were assessed. We investigated minor and major depression (mMD) occurred at 1st, 3rd and 6th months post-partum. Logistic regression models were used to estimate the association between PD, family history for PD and PPD.Forty women had mMD in the post-partum. PD during pregnancy (RR=4.25; 95%CI:1.48-12.19), a history of PD (RR 2.47; 95%CI:1.11-5.49) and family history for PD (RR=2.1; 95%CI:1.06-4.4) predicted PPD after adjusting for lifetime depression and risk factors for PPD.The response rate is moderately low, but it is similar to other studies. The drop out rate is slightly high, however the 600 women who completed the 6th month follow-up did not differ from the presence of PD at baseline.PD is an independent risk factor for PPD, underscoring need to assess PD symptoms during pregnancy. Furthermore, PD represents an important risk factor for the development of PPD and should be routinely screened in order to develop specific preventive interventions.

OBJECTIVE: The aim of the present study was to compare health-related quality of life (HRQoL) measures in euthymic patients with bipolar I and II disorder. We included as comparison samples a group of subjects with recurrent major depression (RMD) and a group of non-psychiatrically ill individuals. METHOD: HRQoL was assessed using the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36) in 253 subjects recruited in 5 Italian centers: 90 patients with bipolar I disorder, 52 patients with bipolar II disorder, 61 subjects with RMD, and 50 healthy comparison individuals. All subjects were evaluated with the Structured Clinical Interview for DSM-IV; psychiatric patients had to be in a euthymic state for at least 2 months prior to the inclusion in the study, as confirmed by a Hamilton Rating Scale for Depression total score < 8 and a Young Mania Rating Scale total score < 6. Data were drawn from a study that was performed from May 2003 to December 2004. RESULTS: When we compared the bipolar and RMD groups with the control group of non-psychiatrically ill individuals and controlled for differences in mean actual age, both bipolar subgroups and subjects with RMD had lower SF-36 mean scores on several subscales; differences in mean SF-36 scores were also detected between bipolar subtypes: bipolar II patients showed HRQoL that was poorer than that of bipolar I patients, even after controlling for age, age at onset, and length of illness, and equal to that of RMD subjects. CONCLUSION: Our study provides evidence that bipolar type II is associated with poorer HRQoL compared to type I even during sustained periods of euthymia and excluding residual symptoms. Interventions targeting rehabilitation and/or functional enhancement may be helpful to improve HRQoL, especially among patients with bipolar II disorder.

In these last years, emotions and feelings, such as attachment, couple and parental bonding and even love, typical of higher mammals, neglected for centuries by experimental sciences, have become the topic of extensive neuroscientific research in order to elucidate their biological mechanisms. Several observations have highlighted the role of monoamines and of neuropeptides, in particular oxytocin, vasopressin and opioids, but this is only the beginning of the story. Love, the most typical human feeling, can be viewed as a dynamic process that represents the result of different components probably subserved by distinct neural substrates at different times. As such, some steps can be identified, in particular its beginning, which is the process of attraction, followed by the attachment process that, in some cases, can last forever. This paper will make some general speculations on the attraction process, in the light of the experience of the Authors.

SummaryIn an attempt to better delineate demographic and clinical characteristics of mild chronic depressions, 46 outpatients fulfilling DSM III-R criteria for dysthymia were compared with patients suffering from a chronic major depressive episode. The profile obtained from our dysthymic sample matches with those reported by other authors. The comparison between “minor” and major chronic depression was also carried out by subdividing these latter into unipolar - recurrent and single episode - and bipolar depression. Dysthymics showed a bipolar family history closer to that of bipolar chronic major depressives which was significantly higher than that recorded in the other sub-categories.

Abnormalities in different parameters of the norepinephrine system have been widely described in major depression. The presence of alpha(2)-adrenoreceptors in blood platelets, similar to those in the brain, prompted us to evaluate them in depressed patients, as compared with healthy controls.Fifteen outpatients affected by major depression, according to DSM IV criteria, and 15 comparable healthy control subjects, were included in the study. The alpha(2)-adrenoreceptors were measured by means of the specific binding of [(3)H]rauwolscine, a highly selective antagonist for this receptor subtype. The severity of depression was assessed by means of the Hamilton Rating Scale for Depression (HRSD).The results did not show any difference in [(3)H]rauwolscine binding parameters (B(max) and K(d)) between patients and controls. However, in the patients, a significant and positive correlation between B(max), which measures the density of the receptors, and HRSD total score was detected.Therefore, although no change in alpha(2)-adrenoreceptors seems to occur in major depression, the density of these receptors would seem to be related to the severity of depressive symptoms.

The aim of this study was to evaluate exercise performance in patients affected by anorexia nervosa.We studied 19 patients (all females, mean age 23.1 +/- 5.2 years) affected by anorexia nervosa (mean weight 37.3 kg, body mass index 14.04 +/- 1.4 kg/m2) and 20 constitutionally thin women, matched for age, height and physical activity, with a body mass index19 kg/m2. All these women underwent clinical examination, standard ECG and a cardiopulmonary stress test.Patients affected by anorexia nervosa showed a lower heart rate and systolic blood pressure at peak exercise (148.8 +/- 13.8 vs 171 +/- 9.2 b/min, p0.001, and 130 +/- 9.5 vs 152 +/- 11.2 mmHg, p0.001), work load (85.5 +/- 15.1 vs 117.2 +/- 20.3 W, p0.001), rate-pressure product (19 371 +/- 2391 vs 25,986 +/- 2218 b/min/mmHg, p0.001), oxygen uptake (VO2) at rest and maximum VO2 (5.4 +/- 1.7 vs 7.1 +/- 1.1 ml/kg/min, p0.001, and 28.08 +/- 6.3 vs 40.2 +/- 7.1 ml/kg/min, p0.001), anaerobic threshold (15.7 +/- 1.9 vs 20.4 +/- 2.1 ml/kg/min, p0.001), VO2 during exercise (9.5 +/- 1.2 vs 12.8 +/- 1.3 ml/min/W, p0.001), maximum minute ventilation (34.5 +/- 9.9 vs 48.4 +/- 10.3 /min, p0.001), and oxygen pulse (7.2 +/- 2 vs 10.9 +/- 2.4 ml/b, p0.001).These data show an abnormal working capacity and cardiovascular responses to exercise in patients affected by anorexia nervosa. The low VO2, both at rest and during exercise, allows them to maintain a relatively high level of physical activity, which contributes to increase the energy expenditure needed for weight loss.

Different findings suggest that the serotonin (5-HT) system may be involved in both the regulation of aggression and the pathophysiology of obsessive-compulsive disorder (OCD). Our study aimed to evaluate the aggressive features of a group of OCD patients and to explore possible correlations with a serotonergic marker, namely platelet 5-HT transporter. Psychopathological and biological patterns were compared with those of a group of healthy controls and those of patients with major depression. Twenty-one patients affected by OCD, 21 by depression and 21 healthy controls were included in the study. Aggressive features were measured by means of the Buss and Durkee Hostility Inventory (BDHI). The platelet 5-HT transporter was evaluated by means of the (3)H-paroxetine binding parameters (maximum binding capacity, B(max) and dissociation constant, K(d)). The OCD patients showed a total score on the BDHI not significantly different from that of healthy controls and lower than that of depressed patients. The factor profile was similar in the 3 groups, but higher in the depressed patients. The irritability, resentment, guilt, negativism and suspiciousness factors were significantly more pronounced in depressed patients. Some sex-related difference in single factors were also observed. The B(max) of (3)H-paroxetine binding was lower in OCD patients than in depressives or healthy controls. OCD patients were more similar to healthy controls than to depressed patients with regard to aggressive features measured by means of the BDHI. This suggests that aggression in OCD is a complex phenomenon that probably requires specific instruments of evaluation.

The selective serotonin reuptake inhibitor sertraline has been shown to be efficacious and well tolerated for the treatment of major depressive disorder. Relatively few trials, however, have examined the role of pharmacotherapy in dysthymia without concurrent major depression. The current investigation focuses on the use of sertraline for the treatment of dysthymia.In this 12-week, multicenter, double-blind study, 310 patients with a DSM-III-R diagnosis of dysthymic disorder without concurrent major depression were randomly assigned to receive either sertraline (N = 158) or placebo (N = 152). Sertraline was initiated at a dose of 50 mg daily, with titration permitted to a maximum of 200 mg daily. The primary evaluation criteria were the Structured Interview Guide for the Hamilton Depression Rating Scale, Seasonal Affective Disorder Version (SIGH-SAD), the Montgomery-Asberg Depression Rating Scale (MADRS), and the Clinical Global Impressions-Severity of Illness (CGI-S) and -Improvement (CGI-I) scales.Mean percentage reductions for the intent-to-treat population in SIGH-SAD scores were 44.6% for the sertraline-treated group and 33.2% for the placebo-treated group (p = .03); MADRS scores, 43.6% and 33.0% (p = .02); and CGI-S scores, 32.8% and 22.8% (p = .02). A significantly greater proportion of the sertraline-treated group was classified as responders (defined for HAM-D and MADRS scores as a 50% score reduction and for CGI-I as a score of 1 or 2 by the final visit) and remitters (SIGH-SAD scoreor = 8) relative to the placebo-treated group by the final visit. In addition, sertraline-treated patients experienced greater improvements in all 9 domains of the Battelle Quality of Life Questionnaire than placebo-treated patients did, with a significant difference observed in favor of sertraline in 8 of the 9 domains. The life satisfaction and social interaction quality of life domains showed significantly greater response in sertraline responders compared with placebo SIGH-SAD responders. Sertraline was well tolerated. Thirteen percent of the sertraline-treated group versus 8% of the placebo-treated group withdrew from therapy owing to adverse events (p = .14).Sertraline is efficacious and well tolerated in the short-term treatment of dysthymia without concurrent major depression.

To validate and clinically characterize mixed bipolar states derived from the concepts of Kraepelin and the Vienna School and defined as sustained instability of affective manifestations of opposite polarity--that usually fluctuate independently of one another--in the setting of marked emotional perplexity.Our criteria for mixed states represent a modified "user-friendly" operationalization of these classical concepts. We compared 143 mixed state patients, so defined, with 118 DSM III-R manic patients, systematically evaluated with the Semistructured Interview for Depression (SID) in our in-patient and day-hospital facilities.The two groups were comparable from demographic and familial standpoints (including family history for bipolar disorder). Mixed states were predominant in the past history of index mixed patients who were more likely to have experienced stressors and to have attempted suicide; manic and hypomanic episodes were more common in the past history of the index manic patients who, in addition, had more episodes and hospitalizations. Although rates of chronicity and rapid cycling were not significantly different in the two groups, the modal episodes in the mixed states were 3-6 months, and in mania they were less than 3 months. Two thirds of both groups arose from a dysregulated baseline temperamental dysregulation, which in manics, was largely hyperthymic, and in mixed patients, was both hyperthymic and depressive. Of our 143 mixed states, only 54% met the DSM III-R criteria for mixed states (which conformed to "dysphoric mixed mania"); of the remaining, 17.5% could be described as "mixed agitated psychotic depressive states" with irritable mood and flight of ideas, and 26% as "unproductive-inhibited manic" with fatigue and indecisiveness. The family history and course of these "non-DSM III-R" mixed states were essentially similar to DSM III-R mixed states.Family history could not be obtained blind to clinical status in patients with severe psychotic mood states.These data favor the classical European approach to mixed states over the grossly under-inclusive current official diagnostic systems.The phenomenology of mixed states is more than the mere superposition of opposite affective symptoms and, in many instances, it represents an expansive-excited phase intruding into a depressive temperament, and a melancholic episode intruding into a hyperthymic temperament.

The similarities between the serotonin (5-HT) transporter in both human platelets and human brain permit us to investigate this structure in patients with different psychiatric disorders. Several reports have shown abnormalities of the 5-HT transporter, by means of the measurement of the 5-HT uptake or of the 3H-imipramine binding, in platelets of patients with obsessive-compulsive disorder (OCD). The availability of the ligand 3H-paroxetine, a selective 5-HT reuptake inhibitor, to label the 5-HT transporter, promoted us to evaluate the binding of 3H-paroxetine in platelets of 18 drug-free patients with OCD. The results, showing that the patients had a lower number of 3H-paroxetine sites, which is inversely correlated with the Yale Brown Obsessive-Compulsive Scale total score, than a similar group of controls, add supporting evidence to the involvement of 5-HT in OCD. In addition, the decreased functionality of the 5-HT transporter seems to be linked to the severity of OC symptoms.

The 3alpha-hydroxy metabolites of progesterone (P), 3alpha-hydroxy-5alpha-pregnan-20-one (allopregnanolone, A-PREG) and 3alpha-hydroxy-5beta-pregnan-20-one (pregnanolone, PREG), have been found to be among the most potent ligands of gamma-aminobutyric (GABA)-A receptors; in experimental animals, they have been found to have anxiolytic, hypnotic and anticonvulsant effects. Similar to those of the benzodiazepines and barbiturates that interact with GABA-A receptors. The present study was undertaken to determine plasma A-PREG and PREG concentrations in the luteal phase in women with partial epilepsy, in order to determine if an impaired metabolism of P occurs in this convulsive disorder. We measured plasma P, A-PREG and PREG levels in 15 women with partial epilepsy in the intercritical phase, and in 15 age-matched healthy women, during the luteal phase of the ovarian cycle (22nd-24th day). The mean plasma +/- S.E. A-PREG levels (three blood samples) were 0.7 +/- 0.6 ng/ml in the epileptic women and 0.5 +/- 0.2 ng/ml in controls, with no significant difference between the two groups (p = NS); the PREG levels were also similar (1.4 +/- 1 ng/ml and 1 +/- 1.1 ng/ml, respectively: p = NS). A significant correlation was found between P levels and both A-PREG and PREG levels (r = 0.72, p0.001 and r = 0.79, p0.001, respectively). There were no significant differences between the two groups in terms of serum adrenocorticotropic hormone, cortisol, dihydroepiandrosterone-sulfate, follicle stimulating hormone, prolactin, luteinizing hormone or estradiol levels.

An eight-week double-blind, multicentre study was performed to evaluate the efficacy and safety of sertraline vs. fluoxetine in the treatment of major depression (DSM-III-R). There were 108 out-patients, from nine Italian centres, entered into the study, of whom 88 were evaluable (48 sertraline, 40 fluoxetine). The final mean daily dose of sertraline was 72 mg and for fluoxetine it was 28 mg. Both treatment groups showed a statistically significant improvement from baseline at one week, and this was maintained until the end of treatment for all of the following measures: Hamilton Rating Scales for Depression and Anxiety, the Montgomery Asberg Depression Rating Scale, Clinical Global Impressions Scale, Zung Self-Rating Scale for Anxiety and the Leeds Sleep Evaluation Questionnaire. Although there was a numerical advantage for sertraline on several efficacy measures, there was no statistically significant difference found between the treatment groups. The incidence of adverse events was similar for both treatments; 40.4% for sertraline and 39.3% for fluoxetine. However, adverse events were generally rated by patients as of lower severity in the sertraline group. In addition, for the fluoxetine group, there was a higher incidence of agitation, anxiety and insomnia than for sertraline. Sertraline was considered to be better tolerated than fluoxetine overall, since only 9.6% of sertraline-treated patients discontinued treatment due to therapy failure whereas in the fluoxetine-treated group this figure was 19.6%. By contrast, 13.5% of sertraline-treated patients discontinued prematurely because of clinical improvement, compared with 10.7% of fluoxetine-treated patients.

An extreme variability and polymorphism in the clinical picture, a frequency of psychotic features, prolonged duration, and resistance to lithium treatment often conceal the affective nature of bipolar mixed episodes, leading to a misdiagnosis of schizophrenia. The extent of the unsolved diagnostic dilemmas is reflected in the latest edition of the formal classificatory systems, DSM-III-R (American Psychiatric Association 1987) and ICD-10 Draft (1989), where the mixed state appears as the vaguest category of mood disorders, with inadequate diagnostic criteria. These criteria do not allow distinction from rapid cycling, nor the recognition of a mixed episode at the onset of bipolar illness; they ignore the low-grade forms and do not encompass the variable and shifting symptomatology, leaving the boundary with most mental disorders, from the neurotic to the schizophrenic, quite fluid. The longitudinal criterion may be useful in many of these conditions: family history, the previous course, characterized by typical mood episodes, usually depressive, alternated with intervals free from psychopathologic symptoms, generally allow the identification of the affective nature and guide us towards a correct interpretation of these forms.

We evaluated in an open trial the safety and effectiveness of a high-potency neuroleptic (bromperidol) for the treatment of AIDS-related organic mental syndromes. Eleven (nine men and two women) seropositive patients with psychotic features were included; six were intravenous drug users (IVDU) and five were not IVDU (NON-IVDU). On the basis of the achievement of a CGI score of 1 or 2 (much improved or very much improved) at the fourth week, nine patients were considered responders, one was a partial responder and one was a non-responder. From a clinical point of view, "positive" psychotic symptoms had a significant remission, while the "negative" ones seemed to be less sensitive or insensitive to bromperidol treatment.

Anxiety and mood disorders are among the psychic afflictions which tend to lead to prolonged benzodiazepine intake. This is also one of the reasons why doctors are faced with a difficult task when having to differentiate between these phenomena and the anxiolytic withdrawal syndrome. Since preexisting psychiatric pathology may modify withdrawal symptoms, thus making differential diagnosis between withdrawal syndrome and recrudescence of the previous disorder even more difficult, it is necessary carefully to assess clinical phenomenology both in relation to its course and to its variability with possible emergence of new symptoms. In addition to drawing attention to the diagnostic elements that can be most useful for identifying the withdrawal syndrome in mood disturbances and panic attack disorder, the authors also report the data of an experimental study of benzodiazepine withdrawal in patients suffering from generalized anxiety.

Benzodiazepines (BDZ) are widely prescribed in clinical practice for many pathological conditions, because of their anxiolytic, sedative, myorelaxant and anticonvulsant properties. The effectiveness, specificity and rapidity of action, the few side effects and the virtual absence of toxicity, have contributed to the widespread use of these compounds. In the last decade, however, the attitude towards BDZ has greatly changed, due to growing awareness and concern about dependence liability, withdrawal phenomena, and long-term side effects. Withdrawal symptoms have been singled out and specified in the contest of a well-defined syndrome with foreseeable onset, duration and remission. Psychic and physical symptoms and disorders of sensory perception can be observed. These manifestations can be suppressed by resuming treatment. The symptomatic and developmental aspects of BDZ withdrawal syndrome are discussed, according to the available literature, with particular reference to clinical features of patients suffering from anxiety and mood disorders.

Pharmacological and biochemical studies indicate that for many receptors, distinct subtypes exist; the multiplicity and diversity of signal reception proteins increase the information-handling capacity of neurons, thus contributing to neural plasticity. This is also the case for the allosteric modulatory-centre omega of the GABA-A receptor. Binding studies suggest the presence of at least two pharmacologically distinct omega receptors in the human brain; furthermore, molecular biological studies have confirmed the existence of genes encoding different omega subtypes. As omega receptors are the site of action of benzodiazepines and other anxiolytic compounds, this knowledge may be useful for developing new subtype-specific drugs, with more selective therapeutic effects.

In an attempt to clarify the possible mode of action of nefopam, a new analgesic compound, the authors tested its effects on imipramine (IMI) binding to platelet membranes. The results showed that nefopam exerted a concentration-dependent inhibition of IMI binding, with a potency comparable to that of tricyclic antidepressants. This finding suggests a possible intervention of serotonergic mechanisms in nefopam-related analgesia.

The authors reviewed pharmacologic treatment of generalized anxiety disorder (GAD), particularly treatment with benzodiazepine agents, and compared the antianxiety effects and dependence risks of these agents with those of nonGABAergic compounds such as buspirone--a new psychotropic drug--in the treatment of chronic anxiety. Forty outpatients who met DSM-III criteria for GAD were randomly assigned to double-blind treatment with buspirone or lorazepam. After 8 weeks, treatment was abruptly stopped and withdrawal reactions were evaluated at Weeks 9 and 10. After 3 to 4 weeks, buspirone's efficacy in treating GAD symptomatology was found to be comparable with lorazepam's, except for sleep disturbances, which were minimally affected by buspirone. After treatment was discontinued, buspirone-treated patients were free from withdrawal symptoms, while the symptoms of lorazepam-treated patients worsened at Week 9.

All of us who had the opportunity of meeting Max Hamilton were agreeably surprised by his sense of moderation matched by his sense of humour. In spite of the widespread use made of the rating scales he created, and the fact that they are generally accepted as standard reference instruments, and in spite of the important role that these rating scales have had, not only on psychopharmacology but also in the fields of research and of clinical practice, he always retained a critical attitude. His philosophy and modesty are clearly shown by a sentence he used frequently: “I always check and firstly I check myself.”

Physiological anxiety is a biological warning system triggered in situations perceived as potentially dangerous. Anxiety becomes pathologic when it occurs without objective reasons, or when its manifestations are excessive in intensity and lenght. Although physiologic and psychologic features of anxiety have been studied extensively, the biochemical mechanisms remain mostly unknown.

A double blind between-groups trial was carried out to compare the effectiveness of the new benzodiazepine compound, bromazepam, (Lexotan, Ro 5-3350) as an anti-anxiety compound with that of diazepan. The fifty-eight psychoneurotic inpatients admitted to the trial were divided into two groups, "obsessives" and "neurotics", in order to assess any specific action of the drug. Assessment was made by means of B.P.R.S. of Overall and Gorham, R.S.A.S. of Hamilton, P.R.S. of Wittenborn and I.M.P.S. of Lorr. The results showed that bromazepam has a general therapeutic effectiveness (though not always as great as that of diazepam) as an anti-anxiety agent, while no difference in the effects of the two drugs was found between the two psychopathologic groups; with both treatments the "obsessives" responded less than the "neurotics". Detailed evaluation of the individual items of the I.M.P.S. showed that bromazepam is likely to exert a disinhibiting or "activating" action, unlike most other benzodiazepines in clinical use.

The state of clinical and research psychopharmacology is analyzed from a historical perspective. Certain social forces have been seen as changing the climate in which research is performed and care delivered. Particular interest exists in the homogenization of multicenter international trials, and with this in mind we briefly present some of our present methods of Data Documentation, Diagnostic Classification, and hopes for future international collaboration.

S-adenosyl-L-methionine (SAMe) is a naturally occurring molecule discovered by Cantoni (8, 9) and found in mammals. The molecular weight is 399.4 and the structural formula is as shown here: Open image in new window