Obsessive compulsive disorder (OCD) often coexists with major depression (MD), with rates varying from 35 to 75%. The nature of the depressive symptomatology can be investigated by familial aggregation analysis, assuming that the disorder which occurs first is the one showing greater genetic liability and should have higher familial concentration. Therefore, the aim of our study was to assess the familial loading for OCD and mood disorders in the families of OCD patients with different chronology of onset for the mood disorder, to evaluate how the familial pattern of the diseases differs with different temporal sequences in which the two syndromes occur. A total of 172 OCD patients entered the study; 112 were pure OCD probands, 12 were unable to separate the onset of the two syndromes, 11 had prior mood disorder, and 37 of them had experienced their first depressive episodes after the onset of OCD. Information about the family history was collected by means of the Family History-Research Diagnostic Criteria (FH-RDC) and by directly interviewing at least 2 relatives per family. Morbidity risks for OCD indicate a familial concentration of the disorder in all groups, except the MD/OCD group. We found the highest rate of relatives affected by mood disorders in the families of patients with first onset of MD (28.8%), whereas in the other 3 groups MRs were much lower. These results suggest the affective nature of OCD patients who experienced first onset of MD. Thus, the chronology of onset seems to identify 2 different typologies of familial distribution.

Controversial results possibly suggesting an association between Tourette's Syndrome (TS) and excess of homozygosity at a Msc I polymorphism in the Dopamine D3 receptor (DRD3) gene have recently been reported. Since a relationship between Obsessive-Compulsive Disorder (OCD) and Tourette's Syndrome (TS) has been suggested, in this study we assessed the frequency of this 2-allele polymorphism in a sample of 97 OCD patients and in 97 control subjects. No statistically significant differences in allele or genotype frequencies were found. Thus this mutation in the coding sequence of the DRD3 gene is unlikely to confer susceptibility to OCD.

SummaryWe calculated Morbidity Risks (MR%) for the major psychiatric conditions in the families of three groups of patients, affected by Eating Disorders (ED; n = 41), Obsessive Compulsive Disorder (OCD; n = 70) and Mood Disorders (MD; n = 39). Our aim was to verify the hypothesis of a common familial pattern of aggregation. Familial risk of developing OCD was significantly increased in the families of OCD probands. Homotypic cases were also augmented in ED and MD families with respect to the rates of the general population, although without statistical significance in the crosswise comparisons. These results confirm the existence of a genetic susceptibility to the development of OCD.

Some studies suggest a relationship between obsessive-compulsive disorder (OCD) and Gilles de la Tourette's syndrome. The pathophysiology of the latter may involve the dopamine system. We screened three important exons of the dopamine D2 receptor (DRD2) gene for mutations in a group of OCD patients with or without tics. No structural changes were found, suggesting no relationship between DRD2 and OCD. Moreover, the frequency of the polymorphism in exon 6 was different from that found in schizophrenics.

SummaryWe assessed the lifetime prevalence of major depression in a sample of 145 patients with a current diagnosis of panic disorder and/or social phobia. The prevalenee tended to be higher in patients with both diagnoses. Patients with panic disorder and social phobia had an earlier onset of the former condition. Familial rates of panic were higher in patients with pure panic disorder, and the rate of depression was increased in relatives of probands who had a lifetime diagnosis of depression.

One hundred and one patients with Panic Disorder/Agoraphobia and forty controls were assessed for DSM-III-R Axis II Disorders and for familial risks for Anxiety and Mood Disorders. Cluster C was the most represented in panic patients; Cluster B was also highly represented. The most common PD among patients were Histrionic, Dependent, and Avoidant. We also found significantly more first-degree relatives with Panic Disorder in the families of panic patients. The presence of PD in the proband did not influence the distribution of the risk for Panic Disorder in the families. The results may suggest that the individual liability to panic is more likely to depend on familial factors than on individual patterns of pathologic personality.

SummaryThis study presents the clinical and demographic characteristics of a sample of 131 patients, who met DSM III-R criteria for obsessive-compulsive disorder (OCD). Our aim was to compare our epidemiological data with non-European research, and to investigate the relationship between OCD symptoms and other clinical features, ie other Axis I concomitant disturbances, personality disorders (Axis II) and family history. Furthermore, we evaluated the age at onset distribution according to sex, family history and presence/absence of a comorbid diagnosis of mood disorder, by means of survival analysis.

*Departement of Neuropsychiatric Sciences, S. Raffaele Hospital, University of Milan, School of Medicine

Immunological, neuroendocrine and psychological parameters were examined in 14 psychophysically healthy subjects and in 17 panic disorder patients before and after a 30-day course of alprazolam therapy. T lymphocyte proliferation in response to the mitogen phytohemagglutinin, lymphocyte beta-endorphin (beta-EP) concentrations, plasma ACTH, cortisol and beta-EP levels were examined in basal conditions and after corticotropin-releasing hormone (CRH) stimulation. Cortisol inhibition by dexamethasone (DST) and basal growth hormone (GH) and prolactin levels were also examined. Depression, state or trait anxiety, anticipatory anxiety, agoraphobia, simple and social phobias, severity and frequency of panic attacks were monitored by rating scales. The immune study did not reveal any significant difference between patients and controls, or any effect of alprazolam therapy. The hormonal data for the two groups were similar, except for higher than normal basal ACTH and GH plasma levels, lower than normal ratios between the ACTH and cortisol responses to CRH, and blunted DST in some patients. All the impairments improved after alprazolam therapy, in parallel with decreases in anxiety and in severity and frequency of panic attacks.

The rate of comorbid diagnoses in a group of 92 patients with obsessive-compulsive disorder (OCD) was examined, with particular attention being paid to mood disorders. The family history method was used to study the frequency of psychiatric disorders in the patients' families and to analyze the characteristics of the familial loading for OCD and mood disorders. A comorbid diagnosis of mood disorder occurred in 35.9% of the patients. The morbidity risk for OCD in the patients' families accounted for 3.4%; when 21 patients with an age of onset under 14 were examined, the morbidity risk in first degree relatives reached 8.8%. This tendency did not appear to be true for mood disorders.

We analyzed the familial morbidity risk for mood disorders (MR) and the presence of a family history of alcoholism in a group of 58 patients with DSM-III borderline personality disorder (PD). The MR in the families of borderline subjects was not significantly different from that found in a control group of affective patients with other cluster II PD, or without PD. The MR in the families of borderline subjects who had never developed an affective episode was not significantly different from that found in the families of borderline PD with a history of mood disorders. Borderline subjects with mood disorders had higher rates of alcoholism in their families, mainly among parents. Our results support the hypothesis that borderline PD, even in absence of the codiagnosis of a mood disorder in the subject, may be a predictor of higher familial liability to mood disorders, although it may be more informative for the familial clustering of specific subgroups than for mood disorders as a whole.

In a study of the families of 21 schizotypal patients, we found an increased morbidity risk for schizophrenia compared with that in the families of 21 nonschizotypal patients and 42 controls. The Axis I diagnoses did not influence the distribution of the morbidity risk in the families of the schizotypal patients. If the schizotypal subjects also had other personality disorders, the morbidity risk for schizophrenia among their relatives was lower, although not significantly.

Forty-eight patients with panic disorder/agoraphobia (PAD) and 30 with obsessive-compulsive disorder (OCD) were assessed for DSM-III-R axis II personality disorders (PD) and the presence of the same anxiety disorder in the relatives of probands (homotypic disorders). No specific personality disorder was present significantly more often in either of the two groups. Agoraphobia was not associated with higher rates of axis II disorders in PAD patients. Duration of illness did not influence the presence of a PD in patients of both groups. Secondary cases of the same anxiety disorder were significantly more common among first-degree relatives of PAD patients. A discriminant analysis performed on the most frequent personality traits of both groups provided a correct classification of cases of 97.4%. Our results do not support the hypothesis of PD as secondary to anxiety disorders and confirm previous findings of a lack of specificity between DSM-III-R axis II categories and OCD and PAD.