Bulimia nervosa with and without obsessive-compulsive syndromes.

The present study was performed in a group of bulimic (BN) females (1) to assess prevalence rates of comorbid obsessive-compulsive phenomena; (2) to investigate whether BN patients display a characteristic cluster of obsessive-compulsive symptoms; and (3) to determine whether obsessive-compulsive symptoms influence the clinical picture of BN. Thirty-eight DSM-IV BN females were interviewed by means of the Structured Clinical Interview for DSM-III-R (SCID) to assess the prevalence rate of obsessive compulsive disorder (OCD); the Yale-Brown Obsessive-Compulsive Symptom Scale (Y-BOCS) Symptom Check-List was also used to evaluate the presence of obsessive-compulsive symptoms. The phenomenology of BN females with obsessive-compulsive syndromes (OCS) as detected by the Y-BOCS was compared to that shown by a "control" group of nonbulimic OCD females. Finally, the eating-related psychopathology of BN women with and without OCS was compared. The current prevalence rates of OCD and of subthreshold obsessive-compulsive syndrome (sOCS) in our sample were 10.5% and 15.8%, respectively. Thus, a total of 26.3% of BN females had a current OCS that comprised both clinical disorders and subthreshold syndromes. No differences were detected between obsessive-compulsive symptoms of these females and those of the control group of nonbulimic OCD females. BN females with OCS had higher ratings on the Eating Disorder Inventory (EDI) total score and on the "drive for thinness" and the "bulimia" items of the scale, as compared to BN females without OCS. In conclusion, it appears that a considerable proportion of BN females display OCS, which sometimes are not severe enough to fulfill diagnostic criteria for OCD. Moreover, in these patients, obsessive-compulsive symptoms are undistinguishable from those of OCD females, and exert a negative influence on the clinical picture of the bulimic disorder.

The cAMP-dependent protein kinase substrate Rap1 in platelets from patients with obsessive compulsive disorder or schizophrenia.

Previous studies have reported that the cAMP-dependent protein kinase and one of its substrates, namely Rap1, are altered in patients with affective disorders. Abnormalities in the cAMP-dependent protein kinase have also been reported in platelets of patients with obsessive compulsive disorder and schizophrenia. However, it remains to be determined whether abnormalities in Rap1 are specifically related to affective disorders or may also be present in schizophrenia and obsessive compulsive disorder. Thus, we investigated Rap1 in platelets from 12 drug-free patients with obsessive compulsive disorder, ten drug-free patients with schizophrenia, and 20 healthy subjects. While no difference was observed in the levels of Rap1 between groups, the phosphorylation state of Rap1 was significantly lower in patients with obsessive compulsive disorder than in schizophrenic patients and controls. These data further support the idea that abnormalities of cAMP signalling pathway could be associated, albeit in a somewhat different way, with several psychiatric disorders.

Lymphocyte peripheral benzodiazepine receptor mRNA decreases in obsessive-compulsive disorder.

The relative content of peripheral benzodiazepine receptor (pBR) mRNA was examined by reverse transcriptase-polymerase chain reaction in lymphocytes of obsessive-compulsive disorder (OCD) patients, according to their clinical course of illness. pBR mRNA significantly decreased only in chronic OCD patients (n=8) as compared to controls (n=10), whereas no significant changes were observed in episodic OCD patients (n=7). We suggest that modulation of pBR gene expression might delineate a clinical heterogeneity in OCD.

Recognition and treatment of dysthymia in elderly patients.

This review focuses on recent literature concerning dysthymia in the elderly population. Epidemiological data and clinical picture, diagnostic and therapeutic issues are evaluated and discussed. Although depressive syndromes are common in older patients, prevalence rates of dysthymia in the elderly are lower than in younger adults. This finding may be the consequence of the diagnostic criteria provided by the Diagnostic and Statistical Manual of Mental Disorders (DSM) which are not specific for older adults. Other factors that complicate making diagnoses of dysthymia in older individuals are comorbid general conditions, cognitive deterioration and disorders, and frequent adverse life events (e.g. bereavement). The effects of these factors should be better defined to clarify whether elderly dysthymia is underestimated and if modified diagnostic criteria should be provided. A few researchers have identified a series of clinical features that are clearly different in the elderly and in young adult patients with dysthymia. These features are particularly related to the late onset and to the peculiar comorbidity of this disorder and suggest that dysthymia is a different disorder in the elderly. Drug treatment of depressive conditions in the elderly is currently based on new antidepressants [selective serotonin (5-hydroxytryptamine; 5-HT) reuptake inhibitors, norepinephrine (noradrenaline) reuptake inhibitors, benzamides]. These agents have an improved adverse effect profile compared with some of the older agents. Moreover, very few systematic studies have been performed using these drugs in samples of older patients with dysthymia and available data do not allow conclusions on drug choice and dosage. Besides, no specific data are available concerning the psychotherapy of dysthymia in this age group. All these topics need to be further investigated in studies comparing the elderly with control groups of younger patients with dysthymia.

Suicide and depression.

Suicide is difficult to predict, has the potential for catastrophic outcome, and is preventable. Although some persons admit freely to feelings of sadness and wishes for their lives to be over, others offer little, if any, overt forecasting of impending self-harm. Many of these same people seek help under other auspices. Approximately two thirds of those who commit suicide had visited a physician during the preceding month. Recognizing the signs and symptoms with which suicide-prone patients present to emergency departments is central to preventing unnecessary death, injury, and disability caused by failed attempts. The common presentations of patients at risk for suicide and some of the psychiatric conditions that carry a risk for suicide are reviewed.

Altered cAMP-dependent protein kinase A in platelets of patients with obsessive-compulsive disorder.

OBJECTIVE: The purpose of this study was to assess cAMP-dependent protein kinase A in patients with obsessive-compulsive disorder (OCD). METHOD: The levels and the activity of protein kinase A were evaluated in whole platelets obtained from 12 unmedicated patients with OCD and 15 healthy comparison subjects. RESULTS: The immunolabeling of protein kinase A regulatory subunits type I and II were significantly greater but that of the catalytic subunit significantly lower in patients with OCD than in healthy subjects. The cAMP-stimulated activity in patients with OCD was significantly lower than that in healthy subjects. CONCLUSIONS: These data suggest a possible role of protein kinase A in the pathophysiology of OCD.

Onset of obsessive-compulsive disorder: premorbid conditions and prodromal phase.

This article focuses on the clinical onset of obsessive-compulsive disorder (OCD), specifically addressing the age of onset, gradual and acute onset, and whether there are some types of premorbid conditions or a prodromal phase that predispose individuals to the onset of OCD. Clinical and epidemiological studies have come to different conclusions regarding age at onset as well as regarding differences between the sexes. Data gleaned from research to date have demonstrated a relationship between OCD and obsessive-compulsive personality disorder (OCPD), although OCPD does not appear to be the more prevalent personality disorder among patients with OCD. Preliminary research has suggested that Axis I disorders may predispose individuals to OCD onset; however, the significance of this relationship remains to be clarified. Evidence of the association between OCD and subthreshold obsessive-compulsive syndrome suggests that these disorders lie on a continuum of severity, with some cases developing OCD while others do not.

The role of recent life events in the onset of obsessive-compulsive disorder.

Although many investigations into the onset of obsessive-compulsive disorder (OCD) suggest the occurrence of potential life events as triggering factors, such an association has not been well studied to date. The purpose of the present paper is to review the literature on OCD onset in order to determine whether OCD is triggered by recent life events, what specific events may serve as triggers, and the clinical and research implications of these factors. Overall, the available studies do not consistently support the theory that OCD is triggered by specific antecedent life events. However, there is a body of evidence to support the theory that the specific life events of pregnancy and birth of a child can trigger OCD. This apparent association has led to the investigation of certain neurohormonal factors, including changes in estrogen or oxytocin levels, that may be of etiopathogenetic significance in OCD. Confirming such associations may allow clinicians to provide more targeted preventive and therapeutic interventions.

Amisulpride in medium-term treatment of dysthymia: a six-month, double-blind safety study versus amitriptyline. AMILONG investigators.

Two hundred and fifty patients participated in a 6-month, double-blind study to evaluate safety and efficacy of a medium-term treatment with amisulpride 50 mg/day versus amitriptyline 25-75 mg/day in dysthymia. Patients in treatment groups (165 amisulpride; 85 amitriptyline) were well balanced for demographic and baseline characteristics. A total of 139 patients (93 amisulpride, 46 amitriptyline) completed the study with no statistically significant differences in reasons for premature termination between the two groups. A tendency towards a higher incidence of treatment-emergent adverse events with amitriptyline was observed (73% versus 64% amisulpride). In the amitriptyline group, a statistically significantly higher incidence of central nervous system (41% versus 24%, p=0.004) and autonomic nervous system disorders (45% versus 16%, p < 0.0001) was reported. Conversely, endocrine disorders were more frequent with amisulpride (18% versus 7%, p=0.023). Efficacy was a secondary end-point. Results of the symptom rating scales indicate that both drugs were equally effective: 60% and 62% of patients under amisulpride and amitriptyline, respectively, achieved a reduction > or = 50% of the Montgomery and Asberg Rating Scale total score at end-point. On the item 'global improvement' of the Clinical Global Impression, 67% of amisulpride and 68% of amitriptyline patients were rated as 'very much' or 'much' improved. Results of the present study in a large patient population further confirm the safe use of amisulpride in dysthymia and support its administration upon a medium-term treatment period.

Delineating psychopathologic clusters within dysthymia: a study of 512 out-patients without major depression.

BACKGROUND: The literature indicates that emotional-cognitive symptoms are much more characteristic of dysthymia than the vegetative and psychomotor symptoms of major depression, yet this is insufficiently emphasized in the official criteria listed in the criteria of the American Psychiatric Association. Furthermore, as previous studies have examined these symptoms more in relation to prevalence than to possible symptom aggregation, in the present analyses we address both aspects. METHODS: In two multicenter collaborative trials, 512 out-patients meeting the symptom criteria of DSM-III-R dysthymia but without major depression were recruited. In this respect they conformed to the conceptual framework of ICD-10 which tends to restrict dysthymia to a subthreshold depression without excursion into severe depressive episodes. The Montgomery Asberg Depression Rating Scale (MADRS) and the Hamilton Anxiety Rating Scale (HAM-A) were used to assess depressive and anxiety symptoms. RESULTS: Symptoms most frequently observed, besides depressed mood (100% by definition), were 'low energy or fatigue' (96%) and 'poor concentration or indecisiveness' (88%), followed by 'low self-esteem' (80%), 'insomnia or hypersomnia' (77%), 'poor appetite or overeating' (69%) and 'feeling of hopelessness' (42%). Interestingly, in the subjects with fewer than five symptoms, the most frequent were low energy or fatigue (93%), poor concentration or indecisiveness (79%) and low self-esteem (77%), the other symptoms being present in no more than half the sample. MADRS factor analysis identified two main factors: the first consisting of apparent and reported sadness, and the second concentration difficulties and lassitude. HAM-A factor analysis identified two factors clearly differentiating somatic and psychic symptoms. LIMITATIONS: Because suicidal patients were excluded on the ground of human subject concerns, our sample is representative of the milder range of symptomatology within the spectrum of dysthymia. This may in part explain the low prevalence of neurovegetative symptoms. CONCLUSION: Despite this, the present study involves the largest sample of pure dysthymia ever studied. Our results indicate that dysthymic disorder appears to primarily involve psychologic symptoms. The psychological symptoms themselves seem to cluster into sadness versus mental fatigue; as for anxiety symptoms, they appear divisible into somatic and psychic clusters, with the latter prevailing in dysthymia. Dysthymia proper, dominated by negative affectivity, might be distinguishable from a 'neurasthenic' subform dominated by low energy or 'deficit' symptoms at mental and physical levels.

Obsessive-compulsive syndromes in older adolescents.

OBJECTIVE: This report presents data on the prevalence of both obsessive-compulsive disorder (OCD) and subthreshold obsessive-compulsive syndrome (sOCS) in a representative sample of older male adolescents living in Piedmont, Italy. METHOD: A total of 1,883 recruits to the Italian Defence Force were interviewed using the OC portion of the Diagnostic Interview Schedule. A diagnosis of sOCS was made for individuals who had obsessive and/or compulsive symptoms but who failed to meet one of the severity criteria of impairment. RESULTS: The point and lifetime prevalence rates of OCD were 2.0% and 2.6%, respectively. In total, 12.3% of the subjects received a current diagnosis of sOCS. No differences were found when examining prevalence rates according to area of residence or occupational status of the subjects. CONCLUSION: Our findings suggest that OCD is as common in older male adolescents as it is in adults, and that sOCS, being commonly endorsed in a general adolescent population, may represent a normal phenomenon in older adolescents.

Gender-related clinical differences in obsessive-compulsive disorder.

The purpose of the present study was to investigate the gender-related differences of clinical features in a sample of obsessive-compulsive (OCD) patients. One hundred and sixty outpatients with a principal diagnosis of obsessive-compulsive disorder (DSM-IV, Y-BOCS = 16) were admitted. Patients were evaluated with a semi-structured interview covering the following areas: socio-demographic data, Axis I diagnoses (DSM-IV), OCD clinical features (age at onset of OC symptoms and disorder, type of onset, life events and type of course). For statistical analysis the sample was subdivided in two groups according to gender. We found an earlier age at onset of OC symptoms and disorder in males; an insidious onset and a chronic course of illness were also observed in that group of patients. Females more frequently showed an acute onset of OCD and an episodic course of illness; they also reported more frequently a stressful event in the year preceding OCD onset. A history of anxiety disorders with onset preceding OCD and hypomanic episodes occurring after OCD onset was significantly more common among males, while females showed more frequently a history of eating disorders. We found three gender-related features of OCD: males show an earlier age at onset with a lower impact of precipitant events in triggering the disorder; OCD seems to occur in a relative high proportion of males who already have phobias and/or tic disorders; and a surfeit of chronic course of the illness in males in comparison with females.

Recent life events and obsessive-compulsive disorder (OCD): the role of pregnancy/delivery.

Conflicting results have been reported on the possible role of life events in triggering OCD onset. Moreover, pregnancy and/or delivery, among life events, appear to influence the OCD course and, in some cases, appear related to its onset. Our purpose was to assess the occurrence of potentially traumatizing events among patients with OCD. The study also provides an initial exploration of the association between OCD and pregnancy or delivery. The number and type of stressful life events which occurred in the 12 months before the onset of OCD were determined for both OCD patients (N = 68, 33 women and 35 men) and a group of comparison subjects (N = 68, 33 women and 35 men) by using a semistructured interview in accordance with Paykel's list. The results did not show a significant excess of life events in patients compared with healthy subjects. No differences were detected between OCD patients according to gender. When examining the type of events, OCD female individuals were found to be more likely than normal female subjects to report exposure to postpartum events, and high rates of obstetric complications were observed in these patients. Subjects with postpartum OCD had significantly higher rates of aggressive obsessions to harm the newborn. OCD male subjects did not show an association between a specific event and onset of the disorder. The findings confirm that the postpartum period represents a risk factor for OCD in some individuals, and suggest that obstetric complications may be relevant to the development of the disorder.

Peripheral benzodiazepine receptor messenger RNA is decreased in lymphocytes of generalized anxiety disorder patients.

BACKGROUND: The aim of this study was to assess whether the decrease of peripheral benzodiazepine receptor (pBR) number in peripheral blood mononuclear cells (PBMC), previously observed in patients with generalized anxiety disorder, is paralleled by changes in the relative content of messenger RNA (mRNA) encoding pBR. METHODS: Eight patients with a DSM-III-R diagnosis of generalized anxiety disorder were examined before, during, and after 2'-chloro-N-desmethyl-diazepam treatment. Eight healthy subjects were analyzed in parallel. The relative content of pBR mRNA was determined by reverse-transcriptase-polymerase chain reaction, using beta-actin as internal standard. Kinetic binding properties of pBR were measured using 3H-PK11195 as a ligand. RESULTS: pBR and pBR mRNA were significantly decreased in untreated generalized anxiety disorder patients as compared to controls (by 45% and 70%, respectively). Both pBR density and mRNA levels returned to control values during treatment or after withdrawal, which also coincided with recovery from anxiety. CONCLUSIONS: These results suggest that the turnover rate of pBR is reduced in PBMC of generalized anxiety disorder patients, and that this change occurs at the transcriptional level.

Paroxetine efficacy in the treatment of generalized anxiety disorder.

Recently, there has been a renewed interest in alternatives to the benzodiazepines for the treatment of generalized anxiety disorder (GAD). The aim of the present study was to compare the efficacy of paroxetine vs. imipramine and 2'-chlordesmethyldiazepam in 81 patients with a DSM-IV diagnosis of GAD. Approximately two-thirds of the patients who completed the study improved greatly or moderately on all three active drugs. During the first 2 weeks of treatment, 2'-chlordesmethyldiazepam treatment resulted in the greatest improvement in anxiety ratings. Both paroxetine and imipramine treatment resulted in more improvement than 2'-chlordesmethyldiazepam by the fourth week of treatment. Paroxetine and imipramine affect predominantly psychic symptoms, whereas 2'-chlordesmethyldiazepam affects predominantly somatic symptoms. Our results suggest that paroxetine is effective for the treatment of GAD.

Episodic and chronic obsessive-compulsive disorder.

Several lines of evidence support the concept of obsessive-compulsive disorder (OCD) as a heterogeneous illness. Using a range of factors such as demographic, psychosocial, and clinical variables, we compared OCD patients with chronic (n = 55) versus episodic (n = 46) courses of illness. Patients were evaluated monthly for 1 year while receiving no treatment. Significant differences in sex ratio, age at onset of the disorder, illness duration, type of symptoms, and familial history were found between the two groups. These findings are consistent with the concept of OCD as a heterogeneous disorder. Patients with an episodic course of the disorder may be a distinct subgroup within the whole group of obsessive-compulsive patients.

Hypothalamic-pituitary-adrenal axis function, psychopathological traits, and natural killer (NK) cell activity in anorexia nervosa.

To evaluate the role of Hypothalamic-Pituitary-Adrenal (HPA) hormones and psychoneuroendocrine modulation on NK cell activity in Anorexia Nervosa (AN) we studied in 24 patients and 20 sex- and age-matched healthy controls, the spontaneous NK activity of peripheral blood mononuclear (PBM) cells and the susceptibility in vitro to cortisol or immune interferon or interleukin-2. NK cytotoxicity of PBM cells was measured in a direct non-radiometric 4h cytolytic assay using K562 cells as targets. HPA axis function was evaluated by IV ovine Corticotropin Releasing Hormone (o-CRH) administration. We did not find clear-cut abnormalities of NK cytotoxicities either in basal conditions or after exposure to challengers. The extent of cortisol-dependent inhibition was comparable in patients and controls. Significant inverse and direct correlations were found respectively between the spontaneous NK cell activity and baseline serum cortisol at 0800 h (r = -0.5; p < .02), and between IL-2 dependent boosting of NK cell cytotoxicity and ACTH, beta-endorphin or cortisol responses after o-CRH, expressed as areas under the curve (AUC) (r = 0.46, p < .05; r = 0.46, p < .05; and r = -0.48, p < .05, respectively). Correlations observed with AUC ratios yielded more significant results (r = 0.62; p < .01 and r = 0.51; p < .05 respectively). These data suggest a role for Proopiomelanocortin (POMC) derived peptides in the regulation of NK cell activity in AN, and multifaceted relationships between this particular immune function, on the one hand, and certain patterns of HPA axis function on the other.

[Description of a case of Cotard's syndrome]. / Sindrome di Cotard. Descrizione di un caso.

The authors report the case of a male 61-year-old patient with Cotard's syndrome. Onset occurred three years ago with depressive symptoms that did not show the specific features of the syndrome, but failed to respond fully to treatment with tricyclic antidepressants. A probable later recurrence was characterised by elements typical of Cotard's syndrome. Treatment with tricyclic and serotoninergic antidepressants was ineffective. Encephalic NMR showed multiple ischemic foci and signs of cortical atrophy. Three years after the onset of depressive symptoms Cotard's syndrome is virtually unchanged and shows ingravescent mental deterioration.

Drug treatment of obsessive-compulsive disorder (OCD): long-term trial with clomipramine and selective serotonin reuptake inhibitors (SSRIs).

A 2-year, open-label followup was performed on 130 obsessive-compulsive patients who were responders to a previous 6-month treatment with clomipramine (150 mg/day), fluoxetine (40 mg/day), or fluvoxamine (300 mg/day). Continuation treatment with the same daily dose was compared to continuation with half doses or to discontinuation of pharmacotherapy. The Yale-Brown Obsessive Compulsive Scale (Y-BOCS) and the Clinical Global Impressions (CGI) scale were used every 3 months, or whenever a worsening of symptoms was experienced. Maintenance treatments were found significantly superior to discontinuation in preventing relapses, and no differences in efficacy were found between full and half doses. A comparison of the three subgroups of patients who were withdrawn from drug therapy failed to demonstrate any statistical difference.

Therapeutic effect and safety of adjunctive risperidone in refractory obsessive-compulsive disorder (OCD).

It has been well established that more than 40 percent of patients with obsessive-compulsive disorder (OCD) do not improve after an adequate trial with serotonin uptake inhibitors (SUIs). The first purpose of this trial was to compare the short-term efficacy and safety of two different strategies in a sample of treatment-refractory OCD patients: dose increase of the ongoing treatment versus the addition of another SUI. The second purpose was to investigate the short-term efficacy and safety of adjunctive risperidone in SUI-refractory OCD patients. Thirty-three OCD patients who were unimproved after a short-term treatment with clomipramine (150 mg/day) were admitted to the study. In the first part of the study, the dose increase of clomipramine was compared with sertraline addition, in an open-label manner. The addition of sertraline to the ongoing treatment appeared to be more effective and tolerable than the clomipramine dose increase. Seven (50%) of the 14 patients who were considered nonresponders after the first part of the study, showed good clinical improvement and good tolerability after risperidone augmentation. These results suggest that risperidone addition to ongoing SUIs may be useful in augmenting pharmacologic response in OCD.