Psychiatric disorders in the relatives of probands with affective disorders. The Yale University--National Institute of Mental Health Collaborative Study.

A family study of psychiatric disorders in 2,003 first-degree relatives of 335 probands found increased rates of bipolar I disorder and major depression (MD) in the relatives of probands with bipolar disorder and increased rates of MD in the relatives of probands with MD. There was a similarity in rates of affective disorders in the relatives of ambulatory and of hospitalized depressed probands (suggesting that ambulatory depressed patients may be as suitable as hospitalized ones for biological studies) and a comparability of rates of illness in relatives between centers for most disorders when comparable diagnostic criteria and procedures were used.

Panic disorder and major depression. Increased risk of depression, alcoholism, panic, and phobic disorders in families of depressed probands with panic disorder.

In a large, case-control family study of depression, 77 (58%) of 133 depressed probands displayed anxiety symptoms that met DSM-III criteria for agoraphobia, panic disorder, or generalized anxiety disorder. In two thirds of these 77 cases, these symptoms were associated with depressive episodes. In a previous study, the lifetime rate of major depression and anxiety disorders among first-degree family members of probands with major depression plus an anxiety disorder was found to be significantly increased regardless of when the anxiety symptoms occurred.

Anxiety disorders and depression: contradictions between family study data and DSM-III conventions.

The authors report data from a case-control family study of lifetime psychiatric diagnoses among the relatives of individuals with major depression. Specifically, they address the relationship between anxiety disorders and major depression. The findings indicate that relatives of individuals with major depression plus an anxiety disorder are at greater risk for major depression, as well as anxiety disorders; than are the relatives of individuals with major depression without an anxiety disorder.

Recent advances in Gilles de la Tourette syndrome: implications for clinical practice and future research.

The clinical presentation and natural history of Gilles de la Tourette syndrome (TS) are reviewed. The waxing and waning of symptoms, the rostrocaudal progression of areas of motor involvement, complex stereotypies, and the familial aggregation of TS and chronic multiple tics are suggestions of underlying neurochemical disturbance; whereas attentional problems, impulsivity and obsessive-compulsive behaviors create interesting links with other disorders. The most robust metabolic findings are the lowered CSF HVA in many TS patients, and the positive response of symptoms to dopamine blockers and clonidine particularly, which would be consistent with dopamine receptor hypersensitivity and possible noradrenergic-dopaminergic interactions in TS.

A family study of schizoaffective, bipolar I, bipolar II, unipolar, and normal control probands.

In a family study of 1,254 adult relatives of patients and controls, lifetime prevalences of major affective disorder (including schizoaffective) were 37%, 24%, 25%, 20% and 7% in relatives of probands with schizoaffective, bipolar I, bipolar II, and unipolar disease, and normal controls. These data were compatible with the different affective disorders representing thresholds on a continuum of underlying multifactorial vulnerability. In this model, schizoaffective illness represents greatest vulnerability, followed by bipolar I and bipolar II, then unipolar illnesses.

Best estimate of lifetime psychiatric diagnosis: a methodological study.

It is important for genetic, epidemiologic, and nosological studies to determine accurate rates of lifetime psychiatric diagnoses in patient and nonpatient populations. As part of a case-control family study of major depression, lifetime psychiatric diagnoses were made for 1,878 individuals. Sources of information used in making diagnostic estimates included direct interview, medical records, and family history data systematically obtained from relatives.

Impaired presynaptic regulation of norepinephrine in schizophrenia. Effects of clonidine in schizophrenic patients and normal controls.

Recent studies have found elevated levels of norepinephrine (NE) in CSF and brain specimens from schizophrenic patients. Presynaptic inhibitory alpha 2-adrenergic receptors regulate NE release in the brain. The hypothesis that the functional sensitivity of this presynaptic regulation of NE is impaired in schizophrenia was tested by evaluating, in schizophrenic patients and age-matched normal controls, the ability of clonidine, an alpha 2 agonist, to lower plasma levels of the NE metabolite 3-methoxy-4-hydroxyphenylglycol (MHPG) and to lower blood pressure (BP).

Clonidine in the treatment of Tourette syndrome: a review of data.

There are conflicting data concerning the efficacy of clonidine in TS. Some TS patients, probably 50% or more, experience substantial, long-term symptomatic improvement with minimal side effects. However, their profile of response is often variable, with behavioral symptoms appearing to show the most consistent improvement.

Assessment of brain function in clinical pediatric research: behavioral and biological strategies.

Psychobiological research in child psychiatry requires rigorous assessment of behavior and multiple perspectives on brain function through neurochemical, neuroendocrine, psychophysiological, and other advanced methods. The serious neuropsychiatric disorders of childhood, such as autism, attention deficit disorder, and language disorders, can be studied in complementary clinical protocols aimed at explicating patterns of behavioral and metabolic dysfunction which characterize various clinical syndromes. Clinical research with children raises sensitive ethical issues; the ethical problems can be addressed when children and families are active collaborators with the investigators and a long-term relationship is established.

Induction of rapid mood cycling during L-dopa treatment in a bipolar patient.

The authors report a longitudinal case study of a woman with a history of bipolar affective disorder in which L-dopa shortened the manic-depressive cycle length when administered in a double-blind trial. This finding suggests a dopaminergic mechanism specifically in changing the frequency of cycling between depression and mania.

Presynaptic adrenergic receptor sensitivity in depression. The effect of long-term desipramine treatment.

Stimulation of presynaptic alpha 2-adrenergic receptors located on norepinephrine (NE)-containing cells in the brain decreases the firing rate and turnover of NE in these neurons. To assess whether abnormalities in the regulation of the NE system during desipramine hydrochloride treatment may be present in depressed patients, the effects of an alpha 2-agonist, clonidine hydrochloride, on plasma levels of the NE metabolite 3-methoxy-4-hydroxy/phenethyleneglycol (MHPG) and on blood pressure (BP) were evaluated in ten depressed patients before and during long-term desipramine treatment. Long-term desipramine treatment significantly attenuated the effects of clonidine on plasma MHPG level and BP, indicating that during desipramine treatment alpha 2-adrenergic receptors had become subsensitive.

Relationship between estimated premorbid adjustment and CSF homovanillic acid and 5-hydroxyindoleacetic acid levels.

The authors completed ratings of premorbid sexual and social adjustment and assays of the CSF homovanillic acid (HVA), 5-hydroxyindoleacetic acid (5-HIAA), and probenecid concentrations in 108 psychiatric patients. Among the 30 patients diagnosed as schizophrenic, poor premorbid sexual adjustment was associated with higher accumulations of HVA in the CSF. No relationship between the estimated premorbid social adjustment and CSF HVA levels was observed.

Covariance of plasma free 3-methoxy-4-hydroxyphenethyleneglycol and diastolic blood pressure.

To test the acute effects of clonidine on plasma levels of 3-methoxy-4-hydroxyphenethyleneglycol (MHPG), the major metabolite of brain norepinephrine (NE), and to examine the relationship between plasma MHPG and concurrently measured blood pressure variables, we performed a series of 31 double blind, placebo controlled, test days in which clonidine (1 and 5 micrograms/kg) or placebo was administered (p.o. at 9:00 a.