Premorbid polysomnographic signs in depressed adolescents: a reanalysis of EEG sleep after longitudinal follow-up in adulthood.

BACKGROUND: This is a report of a clinical follow-up study (10-15 years later as young adults) of adolescent major depressives and normal control subjects. Polysomnographic data were obtained during the original study period when the subjects were adolescent (time 1). With clinical follow-up (time 2) assessments in hand, our objective was to ascertain whether there were any premorbid polysomnographic signs associated with depression during adolescence. METHODS: Based upon initial (during adolescence) and follow-up clinical assessments (as adults), new subject groupings were generated: depression-free normal subjects and original normal subjects who experienced a depressive episode during the follow-up period (latent depressives). Suicidality and recurrence of depression were also examined. Multivariate analysis of covariance was used to analyze group differences in sleep measures and logistic regression for predicting three outcomes: lifetime depression, lifetime suicidality, and recurrence. RESULTS: Comparison of the depression-free normal subjects, the latent depressives, and the original major depressives revealed significant differences for sleep latency and sleep period time. Comparing all lifetime depressives (original major depressives and the latent depressives) to depression-free normal subjects revealed significantly more stages 3 and 4 combined (ST34) sleep and greater sleep period times among the depressives. An analysis involving the presence or absence of suicidality revealed no overall significant differences between the groups. Comparison of the lifetime depressives grouped by nonrecurrent and recurrent depressive course to the depression-free normal subjects revealed significant difference for sleep period time. Using logistic regression, we found that a longer sleep latency and sleep period time significantly predicted lifetime depression. Gender, ST34 sleep, and an interaction term for ST34 sleep and REM latency significantly predicted lifetime suicidality. CONCLUSIONS: There was evidence of premorbid sleep abnormalities during adolescence. A general pattern of sleep disruption around sleep onset and during the first 100 min of the sleep period and overall sleep was evident among the major and lifetime depressives, involving sleep latency (initial insomnia), sleep period time (hypersomnia), REM latency, and slow-wave sleep. This adds to the body of literature that highlights the importance of the first 100 min of the sleep period in depression.

Nocturnal growth hormone secretion studies in adolescents with or without major depression re-examined: integration of adult clinical follow-up data.

BACKGROUND: Early sleep is associated with an increased secretion of human growth hormone (GH) through muscarinic inhibition of somatostatin, a GH suppressant. A clinical follow-up was performed approximately 1 decade after depressed and psychiatrically "normal" control adolescents, who were now young adults, had undergone baseline serial GH measurements over a 24-hour period on the third night of sleep polysomnography studies. METHODS: The study population consisted of 77 young adults who had received a diagnosis of adolescent major depressive disorder and had participated in the adolescent sleep and neuroendocrine studies. Alternatively, the young adult subjects were assessed as normal adolescent control subjects free of any psychiatric diagnosis. Blood samples had been collected for GH every 20 min during the 24-hour period coinciding with the third consecutive night of sleep electroencephalography. Subjects, now in young adulthood, were relocated and blindly reinterviewed using the Schedule for Affective Disorders and Schizophrenia (lifetime version). The original adolescent nocturnal GH data were analyzed in light of the information obtained regarding clinical course into adulthood. RESULTS: A substantial proportion of the nominally normal control group developed at least one episode of major depression or dysthymia during the follow-up period. "Latent" depressive subjects differed from depression-free control subjects by having exhibited a significantly more rapid increase of adolescent nocturnal GH secretion following sleep onset. Of the subjects who had experienced at least one lifetime major depressive episode during the follow-up, the subgroup who would go on to make suicide attempts secreted significantly greater amounts of GH during the first 4 hours of sleep. Adults with lifetime depression exhibited significantly reduced levels of GH in the 100 min preceding sleep onset during adolescence. CONCLUSIONS: Assignment of subjects based on longitudinal clinical follow-up into adulthood revealed that the sleep-related GH secretion paradigm has predictive value for future depressive episodes and future suicide attempts. Dysfunction of complex sleep-onset mechanisms may be a premorbid marker of depression and suicidal behavior.

Familial aggregation of delusional depression: re-examination in a recent family study.

BACKGROUND: Delusional (D-MDD) and nondelusional depression (ND-MDD) differ in clinical presentation, biological abnormalities, course of illness, and treatment response. Family data, however, have been less consistent regarding differential risk both for any major depression (MDD) and specifically D-MDD in relatives of D-MDD probands. In an earlier family study, we observed a 1.5-fold increase in rates of any MDD, specificity of transmission of D-MDD, and increased rates of bipolar disorders in relatives of D-MDD compared to relatives of ND-MDD probands. In a new family study, we attempted to replicate these findings. METHOD: A family study of 361 directly interviewed adult first-degree relatives (FDRs) of 163 probands (118 with MDD and 45 screened normal controls) was used to examine familial aggregation of any MDD, D-MDD, and bipolarity by proband delusional status. RESULTS: Compared to FDRs of ND-MDD probands, FDRs of D-MDD probands were at modestly increased risk for any MDD. These results were unaffected by adjustment for proband ascertainment source, comorbidity, or whether probands had chronologically primary MDD. There was a trend toward increased rates of broadly defined bipolarity (bipolar I, bipolar II, or cyclothymia) in FDRs of D-MDD compared to FDRs of ND-MDD probands. CONCLUSION: Results from the present study were broadly consistent with those from our previous work. While other lines of evidence for D-MDD as a distinct subtype are more compelling than family data, it would be of methodologic interest to identify sources of inconsistency across studies in findings concerning the familial aggregation of delusional depression.

Comparison of RDC, DSM-III, DSM-III-R diagnostic criteria for generalized anxiety disorder.

The diagnosis of generalized anxiety disorder (GAD) has been controversial since its inception. It remains unclear whether more stringent diagnostic criteria, such as in DSM-III-R, have improved the validity of GAD. Family studies suggest that GAD aggregates at least weakly in families of probands with GAD, and support the separation of panic disorder (PD) and GAD. Therefore, we can use a family study design to examine the validity of GAD. Independent familial transmission of GAD supports the validity of GAD. We report here the risk of GAD according to RDC, DSM-III, and DSM-III-R criteria in the first-degree relatives of probands from four diagnostic groups: panic disorder, panic disorder with major depression, early-onset major depression (MDD), and normal controls. We did not find an elevated risk of DSM-III or DSM-III-R GAD in the relatives of any of the ill proband groups compared to the relatives of the never mentally ill when controlling for proband comorbidity for GAD. In contrast, RDC GAD aggregates in the first-degree relatives of probands from both of the PD proband groups (with and without MDD) compared to relatives of the normal control group. The inclusion of cases of subsyndromal panic attacks that did not meet the strict RDC for panic disorder as meeting the less restrictive RDC for GAD may partially account for the familial aggregation of RDC panic disorder and RDC GAD. RDC GAD seems to identify one or more syndrome(s) that may be on the familial spectrum of panic disorder. This syndrome may represent a mild or early variant of panic disorder. We also found a trend for RDC and DSM-III GAD to aggregate in the first-degree relatives of the MDD proband group compared to the relatives of the never mentally ill controls. These data suggest that GAD demonstrates more independent familial transmission from PD and MDD when defined by DSM-III-R criteria than when defined by RDC or DSM-III, and thus support the validity of DSM-III-R GAD.

Is the comorbidity between social phobia and panic disorder due to familial cotransmission or other factors?

BACKGROUND: We previously reported significantly elevated rates of social phobia in relatives of probands with panic disorder compared with relatives of other proband groups. This study further investigates the relationship between social phobia and panic disorder. METHOD: This sample is from a family study that included 193 probands from four mutually exclusive groups (patients with panic disorder, patients with panic disorder and major depression, patients with early-onset major depression, and normal controls) and 1047 of their adult first-degree relatives. Best-estimate diagnoses were completed using DSM-III-R criteria. RESULTS: Social phobia and agoraphobia aggregate in the families of probands with panic disorder without major depression. Social phobia frequently co-occurs with panic disorder in relatives, but the risk for comorbidity does not vary across proband groups. CONCLUSIONS: The familial aggregation of social phobia with panic disorder may be explained by the aggregation of panic disorder in relatives of probands with panic disorder combined with the tendency for panic disorder to occur comorbidly with social phobia in individuals.

Clozapine treatment of psychosis in Parkinson's disease: a report of five consecutive cases.

BACKGROUND: Clozapine has gained acceptance as an antipsychotic in treatment-resistant schizophrenia. Its low propensity to induce extrapyramidal side effects makes clozapine an attractive treatment for patients with Parkinson's disease and dopaminomimetic psychosis. Recent evidence demonstrates that Parkinson's patients are exquisitely sensitive to both the antipsychotic and the potential extrapyramidal effects of clozapine. The uncontrolled studies suggest that low-dose clozapine may be efficacious in this population. The dose range, side effect profiles, and length of treatment varied in these reports. METHOD: We report our experience with five patients with Parkinson's disease and psychosis who were treated with clozapine in an open trial. RESULTS: Three patients were successfully treated with clozapine (25-100 mg/day, mean = 66.7 mg) without worsening their parkinsonism. Adverse effects unrelated to the motor disability required discontinuation of clozapine in the other two patients. At 1- to 2-year follow-up, each patient had required increased dosages of clozapine (75-150 mg/day, mean = 125 mg) for continued management of their psychosis and parkinsonism. The higher dose range was well tolerated. CONCLUSION: These results suggest that clozapine may effectively treat psychosis in Parkinson's disease.