Avoidant personality disorder symptoms in first-degree relatives of schizophrenia patients predict performance on neurocognitive measures: the UCLA family study.

Whether avoidant personality disorder symptoms are related to neurocognitive impairments that aggregate in relatives of schizophrenics is unknown. We report the relationship between avoidant personality disorder symptoms and neurocognitive performance in the first-degree relatives of probands with schizophrenia. 367 first-degree relatives of probands with schizophrenia and 245 relatives of community controls were interviewed for the presence of avoidant personality symptoms and symptoms of paranoid and schizotypal personality disorders and administered neurocognitive measures. Relationships between neurocognitive measures and avoidant symptoms were analyzed using linear mixed models. Avoidant dimensional scores predicted performance on the span of apprehension (SPAN), 3-7 Continuous Performance Test (3-7 CPT), and Trail Making Test (TMT-B) in schizophrenia relatives. These relationships remained significant on the SPAN even after adjustment for paranoid or schizotypal dimensional scores and on the TMT-B after adjustment for paranoid dimensional scores. Moreover, in a second set of analyses comparing schizophrenia relatives to controls there were significant or trending differences in the degree of the relationship between avoidant symptoms and each of these neurocognitive measures even after adjustments for paranoid and schizotypal dimensional scores. The substantial correlation between avoidant and schizotypal symptoms suggests that these personality disorders are not independent. Avoidant and in some cases schizotypal dimensional scores are significant predictors of variability in these neurocognitive measures. In all analyses, higher levels of avoidant symptoms were associated with worse performance on the neurocognitive measures in relatives of schizophrenia probands. These results support the hypothesis that avoidant personality disorder may be a schizophrenia spectrum phenotype.

Avoidant personality disorder is a separable schizophrenia-spectrum personality disorder even when controlling for the presence of paranoid and schizotypal personality disorders The UCLA family study.

It is unresolved whether avoidant personality disorder (APD) is an independent schizophrenia (Sz)-spectrum personality disorder (PD). Some studies find APD and social anxiety symptoms (Sxs) to be separable dimensions of psychopathology in relatives (Rels) of schizophrenics while other studies find avoidant Sxs to be correlated with schizotypal and paranoid Sxs. Rates of APD among first-degree Rels of Sz probands, attention-deficit/hyperactivity disorder (ADHD) probands, and community control (CC) probands were examined. Further analyses examined rates when controlling for the presence of schizotypal (SPD) and paranoid (PPD) personality disorders, differences in APD Sxs between relative groups, and whether APD in Rels of Szs reflects a near miss for another Sz-spectrum PD. Three hundred sixty-two first-degree Rels of Sz probands, 201 relatives of ADHD probands, and 245 Rels of CC probands were interviewed for the presence of DSM-III-R Axis I and II disorders. Diagnoses, integrating family history, interview information, and medical records, were determined. APD occurred more frequently in Rels of Sz probands compared to CC probands (p<0.001) and also when controlling for SPD and PPD (p<0.005). Two Sxs of APD were most characteristic of the Rels of Sz probands: "avoids social or occupational activities..." and "exaggerates the potential difficulties..." 65% of the Rels of Sz probands who had diagnoses of APD were more than one criterion short of a DSM-III-R diagnosis of either SPD or PPD. This indicates that APD is a separate Sz-spectrum disorder, and not merely a sub-clinical form of SPD or PPD.

Clinical outcome following neuroleptic discontinuation in patients with remitted recent-onset schizophrenia.

OBJECTIVE: The goal of this report was to examine the clinical course following neuroleptic discontinuation of patients with recent-onset schizophrenia who had been receiving maintenance antipsychotic treatment for at least 1 year. METHOD: Fifty-three volunteer patients with recent-onset schizophrenia who had been clinically stabilized on a maintenance regimen of fluphenazine decanoate for a mean of 16.7 months had their antipsychotic medications withdrawn under clinical supervision. Participants initially entered a 24-week, double-blind crossover trial in which fluphenazine and placebo were administered for 12 weeks each. For those who did not experience symptom exacerbation or relapse during this period, fluphenazine was openly withdrawn; participants were then followed for up to 18 additional months. RESULTS: When a low threshold for defining symptom reemergence was used, 78% (N=39 of 50) of the patients experienced an exacerbation or relapse within 1 year; 96% (N=48 of 50) did so within 2 years. Mean time to exacerbation or relapse was 235 days. When hospitalization was used as a relapse criterion, only six of 45 of individuals (13%) experiencing an exacerbation or relapse who continued in treatment in the clinic were hospitalized, demonstrating the sensitivity of the psychotic exacerbation criterion. CONCLUSIONS: The vast majority of clinically stable individuals with recent-onset schizophrenia will experience an exacerbation or relapse after antipsychotic discontinuation, even after more than a year of maintenance medication. However, clinical monitoring and a low threshold for reinstating medications can prevent hospitalization for the majority of these patients.

Schizophrenia and schizophrenia-spectrum personality disorders in the first-degree relatives of children with schizophrenia: the UCLA family study.

BACKGROUND: This study tested the hypothesis that childhood-onset schizophrenia (COS) is a variant of adult-onset schizophrenia (AOS) by determining if first-degree relatives of COS probands have an increased risk for schizophrenia and schizotypal and paranoid personality disorders. METHODS: Relatives of COS probands (n = 148) were compared with relatives of attention-deficit/hyperactivity disorder (ADHD) (n = 368) and community control (n = 206) probands. Age-appropriate structured diagnostic interviews were used to assign DSM-III-R diagnoses to probands and their relatives. Family psychiatric history was elicited from multiple informants. Diagnoses of relatives were made blind to information about probands' diagnoses. Final consensus diagnoses, which integrated family history, direct interview information, and medical records, are reported in this article. RESULTS: There was an increased lifetime morbid risk for schizophrenia (4.95% +/- 2.16%) and schizotypal personality disorder (4.20% +/- 2.06%) in the parents of COS probands compared with parents of ADHD (0.45% +/- 0.45%, 0.91% +/- 0.63%) and community control (0%) probands. The parents of COS probands diagnosed as having schizophrenia had an early age of first onset of schizophrenia. Risk for avoidant personality disorder (9.41% +/- 3.17%) was increased in the parents of COS probands compared with parents of community controls (1.67% +/- 1.17%). CONCLUSIONS: The psychiatric disorders that do and do not aggregate in the parents of COS probands are remarkably similar to the disorders that do and do not aggregate in the parents of adults with schizophrenia in modern family studies. These findings provide compelling support for the hypothesis of etiological continuity between COS and AOS.

Fluphenazine levels during maintenance treatment of recent-onset schizophrenia: relation to side effects, psychosocial function and depression.

RATIONALE: The utility of fluphenazine levels during maintenance treatment of schizophrenia is still unclear. OBJECTIVES: This study investigated the relationship between fluphenazine levels and a variety of clinical measures during maintenance treatment of schizophrenia. METHODS: Fluphenazine levels, side effects, depression and psychosocial outcome were measured at five time points over approximately 1 year in 59 recent onset schizophrenic patients treated with a maintenance dose of injectable fluphenazine decanoate. Negative symptoms were evaluated at the 1-year endpoint. RESULTS: Fluphenazine levels showed marked intraindividual variability even when measurements were restricted to the second 6 months of treatment, by which time steady state levels should have been achieved. No consistent relationship was found between fluphenazine levels and any of the outcome measures. CONCLUSIONS: The results of this study suggest that fluphenazine plasma levels do not routinely add relevant clinical information beyond that of dose in evaluating potential side effects or negative consequences during maintenance treatment with the decanoate form of the medication.

Depressive symptoms in the early course of schizophrenia: relationship to familial psychiatric illness.

OBJECTIVE: This study examined the relation between the presence of depressive symptoms in schizophrenic patients with a recent first psychotic episode and affective disorders among their relatives. METHOD: Data on depressive symptoms in 70 patients with schizophrenia diagnosed according to the DSM-III-R criteria, who had had a recent first psychotic episode, and psychiatric diagnostic information on 293 of their first-degree and 674 of their second-degree relatives were collected. Depressive symptoms in the schizophrenic probands were examined at the index psychotic episode (at study entry) and systematically over a 1-year follow-through period. The majority of first-degree family members were interviewed in person with the use of semistructured diagnostic interviews. RESULTS: The linear regression findings confirmed the hypothesis that depressive symptoms in the early course of schizophrenia are associated with a family history of unipolar affective illness. CONCLUSIONS: Because depression in the patients was associated with a family history of depression, this suggests that depression in schizophrenia is not solely either a reaction to having had a psychotic episode or part of the recovery process. The findings are consistent with a model in which a familial genetic liability to affective disorder, when present, is viewed a s exerting a modifying influence on the patient's schizophrenic illness to increase expression of depressive symptoms.

Symptom differences among anxiety patients in clinics with differing treatment orientations : a pilot investigation.

Patients with screening diagnoses of DSM-III-R anxiety disorders were surveyed in two clinics, one oriented toward pharmacology, the other toward behavior therapy. Patients in the two clinics were similar on demographic, diagnostic, and treatment variables but dissimilar on severity and composition of symptoms and on the use of medications and medical services. Patients seen in the psychopharmacology clinic reported more physical symptoms and more frequent use of prescription and over-the-counter medications. Patients in the behavior therapy clinic reported more phobic symptoms. Findings may reflect self-selection and/or referral biases toward one or the other type of clinic based on differences in initial symptoms, beliefs in their pathogenesis, and other associated variables. Further study at point of entry and at follow-up may help clarify these differences.

Bupropion in the treatment of bipolar disorders: the same old story?

BACKGROUND: The treatment of bipolar disorders with mood stabilizing agents is complicated by breakthrough episodes of depression. Currently there are no consistently safe and effective medications for these episodes. The authors address the use of bupropion for this purpose. METHOD: Bupropion was added to the treatment regimens of 3 male and 8 female patients who had bipolar disorders as diagnosed by DSM-III-R criteria and were depressed and nonresponsive to current treatment. Ten of the 11 had previously cycled into manic episodes when treated with either a tricyclic antidepressant, fluoxetine, or phenelzine. RESULTS: Seven of the 11 patients had moderate-to-marked improvement after 6 weeks of treatment. A moderate-to-marked improvement continued in 4 of the 11 patients after a mean of 12 months of treatment (range, 0-20 months), justifying the continuation of bupropion. Baseline Global Assessment of Functioning scores, history of previous response to other antidepressants, treatment refractoriness, comorbid diagnoses, bipolar subtype, family history, cycle length, and demographics did not discriminate between bupropion responders and nonresponders. However, 6 of the 11 patients experienced manic or hypomanic episodes that necessitated discontinuation of bupropion. Five of the 6 patients who had manic episodes had been stabilized on lithium and carbamazepine or valproate prior to the addition of bupropion. CONCLUSION: These findings, based on consecutive cases, suggest that bupropion may pose the same risks as other antidepressants in precipitating manic episodes in depressed bipolar patients. The authors conclude that caution should be exercised when using bupropion in the treatment of bipolar disorders.

Interrater reliability of the Structured Clinical Interview for DSM-III-R, Axis II: schizophrenia spectrum and affective spectrum disorders.

Three interviewers (second raters) blindly rated 15 audiotapes each of the Structured Clinical Interview for DSM-III-R, Axis II (SCID-II) administered to the first degree relatives of probands with either DSM-III-R schizophrenia, schizoaffective disorder, or bipolar disorder, for a total of 45 second ratings. Interrater reliability was determined using the intraclass correlation coefficient and ranged from 0.60 to 0.84. The previous studies of the reliability of structured interviews for diagnosing personality disorders are summarized and compared to the present findings. We conclude that the SCID-II can be reliably used to diagnose schizophrenia-spectrum and affective spectrum disorders in the first degree family members of probands with schizophrenic or bipolar affective disorders.

Persistence of fluphenazine in plasma after decanoate withdrawal.

We discontinued fluphenazine decanoate using a double-blind, crossover random order design, in 12 recent onset clinically stable schizophrenics who had been given fluphenazine decanoate 12.5 mg intramuscularly every 2 weeks for at least 1 year prior to drug withdrawal. Each condition (drug or placebo) lasted 12 weeks. Using a radioimmunoassay verified by comparison to a gas chromatographic-mass spectrometric method, plasma fluphenazine levels were measured every 2 weeks during drug continuation and drug withdrawal conditions. No patient relapsed over the 24-week period of the study. Mean fluphenazine levels between drug continuation and withdrawal conditions showed a progressively larger difference over time, although significant differences were not seen until week 8. By week 12 after drug withdrawal, 33% of subjects still showed notable plasma fluphenazine levels. On the basis of our preliminary findings, we suggest that 2-week intervals between injections may be too short and that wider intervals may achieve similar clinical results.

The dexamethasone suppression test in psychotic disorders.

Dexamethasone suppression tests were given to 69 consecutively admitted psychiatric patients. Nonsuppression rates for depression with or without melancholia and for schizophrenia were similar to those previously reported, but for mania and other psychoses the frequencies were higher than expected.