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The dexamethasone suppression test: an overview of its current status in psychiatry. The APA Task Force on Laboratory Tests in Psychiatry.

The dexamethasone suppression test (DST) has had unprecedented evaluation among biological tests proposed for clinical use in psychiatry. It is hypothesized to reflect pathophysiologic changes at the CNS level. The sensitivity of the DST (rate of a positive outcome, or nonsuppression of cortisol) in major depression is modest (about 40%-50%) but is higher (about 60%-70%) in very severe, especially psychotic, affective disorders, including major depression with psychotic as well as melancholic features, mania, and schizoaffective disorder. The specificity (true negative outcome) of the DST in normal control subjects is above 90%, but it varies from less than 70% to more than 90% in psychiatric conditions that often need to be separated from major affective disorders. In dementia the specificity is even lower. In addition, a number of medical conditions, including severe weight loss and use of alcohol and certain other drugs (barbiturates, anticonvulsants, and others), can produce false positive results. Positive initial DST status in major depression does not add significantly to the likelihood of antidepressant response, and a negative test is not an indication for withholding antidepressant treatment. Some recent data suggest that DST-positive depressions (cortisol nonsuppression) are less likely than DST-negative cases (cortisol suppression) to respond to a placebo. If this is confirmed, it would increase the real magnitude of the difference in treatment response between DST-positive and DST-negative depressed patients. Failure to convert to normal suppression of cortisol with apparent recovery from depression suggests an increased risk for relapse into depression or suicidal behavior. Although the clinical utility of the DST as currently understood is limited, in certain specific situations its thoughtful use may aid clinical decision making. The association of an abnormal test result with major affective disorders encourages continued research on the DST.

Bipolar Disorder↗

Negative symptoms of familial schizophrenia breed true in unstable (vs. stable) cerebral-ventricle pedigrees.

A pattern of negative symptoms associated with a high rate of ongoing brain and ventricular instability has been described in a cohort of schizophrenia spectrum probands (patients with schizophrenia, schizoaffective disorder depressed and bipolar, and psychosis NOS) (Garver, D.L., Nair, T.R., Christensen, J.D., Holcomb, J., Ramberg, J., Kingsbury, S., 1999. Differential patterns of premorbid functioning, symptoms and neuroleptic response in stable and unstable ventricular-volume schizophrenia. Neuropsychopharmacology 20, in press). The present study contrasts the prevalence of negative symptoms in first- and second-degree relatives of probands with unstable ventricle volume (UnsVV) and stable ventricle volume (SVV). One hundred and sixteen first- and second-degree relatives of 10 probands were interviewed using the SANS, the 'Characterization of Course: "Pattern of Symptoms"' [from Comprehensive Assessment of Symptoms and History (CASH)], SCID and SCID-II by interviewers blind to the status of the proband. Thirty-five of the 116 family members met DSM-IV criteria for schizophrenia, SA depressed, 'Cluster A' of the SCID-II (paranoid, schizotypal, schizoid personality disorder), psychosis NOS, or psychotic affective disorder. These 35 family members were defined as falling within a 'schizophrenia spectrum' as described by Farmer, A.E., McGuffin, P., Gottesman, I.I., 1987. Arch. Gen. Psychiatry 44, 634-641, but with the addition of DSM-IV affective psychosis. On that basis, the 35 members were considered 'affected family members' (AFMs). The remaining 81 family members were considered unaffected. The 'predominant symptoms of illness' (during the past 2-3 years) for 25 of the 35 AFMs could be characterized according to the 'Patterns of Symptoms' derived from the CASH. Twenty-five of the 35 AFMs were found to maintain a predominant symptom pattern during the course of illness, which could be characterized according to the 'Pattern of Symptoms' as 'predominantly positive' or 'predominantly negative'. Three of the probands had UnsVV; seven had SVV. Of the 35 AFMs, 11 were related to the UnsVV probands, and 24 were relatives of the SVV probands. The nine rated AFMs of the UnsVV probands showed a trend toward higher SANS scores (7.3 +/- 5.1) (mean +/- s.d.) than the 20 rated AFMs of SVV probands (4.3 +/- 5.1) (p = 0.08) at the time of the interview. Eighty-three per cent (eight of 10) of rated affected pedigree members of the pedigrees delineated by probands with UnsVV probands had a predominantly negative symptom course of illness, and 96% (23 of 24) of rated affected pedigree members of the pedigrees with SVV probands had a predominantly positive symptom course of illness during the preceding 2-3 years (p = 0.002). None of the 12 rated affected pedigree members within pedigrees having UnsVV probands were married at the time of the interview; 45% (14 of 31) of affected pedigree members having SVV probands were married (p = 0.004). A psychiatric disorder, characterized by unstable cerebral ventricles and predominant negative symptoms (including avoidance/failure of marital relationships) appears symptomatically to breed true in pedigrees containing schizophrenia-like illnesses.

Adult↗

Schizoaffective disorder and affective disorders with mood-incongruent psychotic features: keep separate or combine? Evidence from a family study.

OBJECTIVE: This study investigated whether the distinction between schizoaffective disorder and affective disorders with mood-incongruent psychotic features as described in DSM-III-R is reflected by aggregation of schizophrenia in the families of probands with the former disorder and aggregation of affective disorders mainly among the relatives of probands with the latter type of disorders. METHOD: The probands were 118 inpatients with definite lifetime diagnoses of DSM-III-R schizoaffective disorder or a major mood disorder with incongruent psychotic features according to structured clinical interviews. Diagnostic information on 475 of the probands' first-degree relatives was gathered through direct interviews (with 80% of the living first-degree relatives) or the family history approach. The rates of affective and psychotic disorders among these relatives were then compared with those among the relatives of a comparison group of 109 interviewed individuals from the general population who were matched on sociodemographic factors to the inpatient probands. RESULTS: With regard to the familial aggregation of schizophrenia, the DSM-III-R distinction emerged as valid. However, the risk of unipolar affective disorders was enhanced in the families of all of the subgroups of patients studied. The unipolar/bipolar distinction in both DSM-III-R diagnostic groups was reflected by distinct patterns of bipolar disorders in the relatives. CONCLUSIONS: The results partly support the DSM-III-R dichotomy of schizoaffective disorder and affective disorders with mood-incongruent psychotic features. Although the differences between these two diagnostic groups were significant, the magnitude of the differences remained relatively modest.

Adult↗

Vulnerability to delusions over time in schizophrenia and affective disorders.

This research used a prospective longitudinal design to study differences in vulnerability to delusions over time in 234 subjects with schizophrenia, schizoaffective disorder, or bipolar or unipolar affective disorder. Patients were assessed at three successive followups over a 7- to 8-year period. Over 60 percent of the schizophrenia and schizoaffective patients assessed experienced delusional activity at one of the three followups. Over 60 percent of the patients who initially had psychotic affective disorders also showed posthospital delusional activity. Significantly more schizophrenia patients than psychotic affective-disordered patients experienced consistent posthospital delusional activity at three successive followups. Unlike the schizophrenia subjects, affective patients showed a significant reduction in delusions after the first followup. After the initial acute psychotic episode that led to hospitalization, psychotic bipolar and unipolar affective patients showed a traitlike vulnerability to episodic delusional activity over time, but schizophrenia patients were vulnerable to more severe delusional activity and to more frequently recurring or sustained delusions. The study results question the views of several major theorists on the importance, persistance, and prognostic significance of delusions in schizophrenia.

Adult↗

Co-morbidity of select anxiety, affective, and psychotic disorders with cannabis dependence in Southwest California Indians.

Cannabis dependence is co-morbid with psychiatric disorders in general population surveys, but whether co-morbidity exists in American Indian populations is unknown. The aim of this study was to assess co-morbidity between cannabis dependence and psychiatric disorders in a community sample of Southwest California (SWC) Indians. Demographic information and DSMIII- R diagnoses, including differentiation of independent and cannabis-induced psychiatric disorders, were obtained using the Semi-Structured Assessment for the Genetics of Alcoholism (SSAGA) developed for the Collaborative Study on the Genetics of Alcoholism (COGA) from 513 SWC Indian adults residing on contiguous reservations. Although SWC Indians in this sample had high rates of cannabis dependence (43% in men and 24% in women), cannabis-induced psychiatric disorders each occurred in 1% or less of the sample. No significant co-morbidity with independent psychiatric disorders was found. In SWC Indians, cannabis dependence may be less etiologically related to psychiatric disorders than in the general population.

Adult↗

Concurrent use of clozapine and valproate in affective and psychotic disorders.

BACKGROUND: This pharmaco-epidemiologic study was undertaken to determine if the combination of clozapine and valproate poses an increased risk of blood dyscrasias, liver function abnormalities, or other side effects and to develop dosing guidelines when the combination is utilized. METHOD: The charts of 55 patients receiving clozapine and valproate concurrently between May 8, 1989, and May 8, 1992, were reviewed to determine the indication for and length of time on each medication, abnormalities in liver function test results, blood cell dyscrasias, seizures, nausea, vomiting, sedation, sialorrhea, and enuresis. In addition, the efficacy of the combination was measured. RESULTS: The combination of clozapine and valproate was efficacious and well tolerated in the majority of patients. Major adverse effects such as blood dyscrasias or seizures were not experienced by the study population. The side effect that led to discontinuation of the combination most frequently was sedation. CONCLUSION: The combination of clozapine and valproate is safe and efficacious.

Adult↗

Subgenual cingulate cortex volume in first-episode psychosis.

OBJECTIVE: Gray matter volume and glucose utilization have been reported to be reduced in the left subgenual cingulate of subjects with familial bipolar or unipolar depression. It is unclear whether these findings are secondary to recurrent illness or are part of a familial/genetic syndrome. The authors' goal was to clarify these findings. METHOD: Volumetric analyses were performed by using magnetic resonance imaging in 41 patients experiencing their first episode of affective disorder or schizophrenia and in 20 normal comparison subjects. RESULTS: The left subgenual cingulate volume of the patients with affective disorder who had a family history of affective disorder was smaller than that of patients with affective disorder with no family history of the illness and the normal comparison subjects. Patients with schizophrenia did not differ from comparison subjects in left subgenual cingulate volume. CONCLUSIONS: Left subgenual cingulate abnormalities are present at first hospitalization for psychotic affective disorder in patients who have a family history of affective disorder.

Adult↗

Affective disorders following stroke.

Numerous studies in stroke patients suggest that the left frontal anterior region may be strategic for depression. However, these findings could not always be replicated. Some authors even deny any etiological contribution of lesion location to depression. The predominant role of the right hemisphere in secondary mania is well recognized. In disorders such as apathy, anxiety, catastrophe reactions and pathological laughing and crying, further studies are needed to determine the potential clinico-topographic correlations. Affective disorders are important to consider in stroke patients, since they may influence neurological recovery and may be responsive to treatment. Remarkable features of emotional behavior, such as disinhibition, denial, indifference, overt sadness and aggressiveness, are not rare during the acute phase of stroke and might be overlooked if not searched for systematically with appropriately designed scales. Some of these early behaviors, such as denial, may relate to the late development of depression, anxiety and other disorders. Systematic studies on large samples of patients may allow to establish which of these acute emotional behavioral changes are markers for the delayed development of mood disorders.

Affective Disorders, Psychotic↗

Schneider-oriented versus Conrad-oriented psychiatric diagnosis in the same German clinic.

The Chair of the University Nervenklinik in Homburg/Saar was held by Klaus Conrad from 1949-58 and by H.-H. Meyer, a former pupil and colleague of Kurt Schneider, from 1962-72. As the catchment area and admission policy of the clinic remained substantially unchanged throughout, comparison of the relative proportions of all admissions allocated to different diagnostic categories in 1949-58 and 1962-72 can be used to elucidate the similarities and differences between Conrad's and Schneider's diagnostic criteria. The results of this comparison indicate that Schneider's concept of schizophrenia was broader than Conrad's, and his concept of manic-depressive depression more restricted. More detailed comparisons are complicated by differences in nomenclature and in the varieties of functional mental illness recognized in the two periods. However, it seems that Conrad's concept of mania was wider only when the atypical schizophrenia-like psychoses diagnosed during the Conrad era were added to the Conrad-oriented cases of mania; when this was not done, the Schneiderian concept of mania was broader.

Adjustment Disorders↗

Mental pain and its relationship to suicidality and life meaning.

Shneidman (1996) proposed that intense mental pain is related to suicide. Relatedly, Frankl (1963) argued that the loss of life's meaning is related to intense mental pain. The first goal of this research was to test Shneidman's proposition by comparing the mental pain of suicidal and nonsuicidal individuals. Meaning in life and optimism are the polar opposites of suicidality and hopelessness, and the examination of these variables in relation to mental pain was undertaken to provide a test of Frankl's proposition. In two studies, a relationship between a newly developed measure of mental pain--the Orbach & Mikulincer Mental Pain Scale, 2002 (OMMP; see also Orbach, Mikulincer, Sirota & Gilboa-Schechtman, 2002)--and suicidal behavior and life meaning were examined. Results confirmed both propositions. Implications for the study of mental pain and suicide are discussed.

Adult↗

Perinatal risk factors for schizophrenia: diagnostic specificity and relationships with maternal psychopathology.

Although a growing body of evidence supports the hypothesis that exposure to obstetric complications (OCs) increases the vulnerability for schizophrenia, some questions remain unanswered regarding the diagnostic specificity and the etiological significance of this association. Associations with a history of OCs have been reported for other severe psychiatric disorders, such as autism, anorexia nervosa, or psychotic affective disorder. Thus, OCs may increase in a relatively non-specific way the vulnerability for a range of severe mental disorders, the expression of this vulnerability depending on the interaction between OCs and other risk factors, such as the genetic liability for specific psychiatric disorder, or exposure to later environmental risk factors. The causal pathway between OCs, maternal psychopathology, and psychotic outcome in the offspring is not fully elucidated. The directions of the associations are often bi-directional, and the mediating variables, if any, are not clearly identified. OCs may have a direct negative impact on fetal brain development, may be on the causal pathway between prepartum maternal depression/exposure to stress and increased risk of schizophrenia, or may indirectly increase the risk of child's later psychiatric disorder by acting as risk factors for maternal postpartum depression. The links and possible interactions between somatic perinatal risk factors and maternal psychopathology in the association with offspring's increased vulnerability for psychosis have to be further explored.

Anorexia Nervosa↗

An 8-year follow-up of patients with DSM-III-R psychotic depression, schizoaffective disorder, and schizophrenia.

OBJECTIVE: The purpose of this study was to investigate the long-term outcome of patients with functional psychoses. The functional status of patients with mood-congruent and mood-incongruent psychotic depression, schizoaffective disorder, and schizophrenia was examined. METHOD: Ninety-two inpatients with nonmanic and nonorganic functional psychoses who had been discharged from the hospital were identified through inpatient records. A blind rater used DSM-III-R criteria to assign research diagnoses to the patients on the basis of the data gathered at admission. Seventy-one patients were located 8 years later, and personal interviews were conducted with them. RESULTS: Baseline diagnosis was a powerful predictor of long-term outcome, even after controlling for age at onset and duration of episode at admission. Patients with psychotic depression had much better outcomes than patients with schizoaffective disorder or schizophrenia. Fourteen (43.8%) of 32 patients with psychotic depression were free from psychosis at follow-up, in marked contrast to those who had schizoaffective disorder or schizophrenia, none of whom had recovered. Patients with schizoaffective disorder could not be distinguished from patients with schizophrenia. CONCLUSIONS: The prognosis of patients with major depression with mood-incongruent features most closely resembles that of depressed patients with mood-congruent features, while patients with DSM-III-R schizoaffective disorder have a prognosis resembling that of schizophrenic patients. Patients with psychotic affective disorders have a much higher likelihood of recovering from psychosis than do schizophrenic patients.

Age Factors↗

Postpartum affective disorders: the manias and depression of childbirth.

Care offered to women with post-partum affective disorders is crucial to their present and future self-concept and their ability to bond with their infant. Nurses working in obstetrical units are becoming more aware of facilitating the natural bonding process and the staffs of psychiatric/mental health professionals also need to take this into account when working with mothers experiencing post-partum affective disorders. Currently there is much exciting basic research in post-partum illnesses and, it is hoped, in the future women will not have to endure extensive emotional trauma during the post-partum period. Meanwhile, it behooves nurses to help affected women and their families to cope with their experiences in the most productive, guilt-free manner.

Adaptation, Psychological↗

The impact of recent undesirable life events on psychiatric disorders in childhood and adolescence.

The timing and number of recent stressful life events occurring in the year before onset of emotional or behavioural disorder was examined in a consecutive sample of children. Overall, events increase the relative risk of psychiatric disorder by 3-6 times. Events occur throughout the 12 months, but tend to cluster in the 16 weeks nearest onset of symptoms. The number of events influences the onset of disorder: cases with multiple events are more likely to have an event within 16 weeks of onset; cases with single events are more likely to have the event 36-52 weeks before onset. Cases whose onset occurs within 4 weeks of an event may have experienced single or multiple events. The results support the concept of additivity of recent stressful events in some cases of emotional and behavioural disorders in childhood.

Adolescent↗

[Role of sex and age in the occurrence and course of attack-like schizophrenia (based on epidemiological study data)].

On the basis of an over-all investigation of 2 districts of Moscow (1548 patients) the authors studied correlations between clinical traits of attack-like schizophrenia and factors of sex and age. It was demonstrated that the disease most frequently (irrespective of the sex and duration) manifests itself by affective-delusional attacks, then go depressive states, acute-delusional oneiroid and manic attacks. The statistical processing of these results demonstrates the existence of a common regularity in the development of clinical traits of attack-like schizophrenia. Factors of sex and age contribute only to conditions of a predilectiveness in an occurrence of different syndromes.

Adolescent↗

Positive and negative symptoms in neuroleptic-free psychotic inpatients.

Andreasen's scales for the assessment of positive (SAPS) and negative (SANS) symptoms and the Brief Psychiatric Rating Scale (BPRS) were administered to a group of 70 neuroleptic-free psychotic inpatients. Individual ratings from the SAPS and SANS, together with the 18-item BPRS, were examined to identify clusters of symptoms. The findings, consistent with our previous studies using medicated patients, did not support a simple positive-negative dichotomy. Independent syndromes representing negative symptoms and thought disorder were apparent, although within the negative syndrome there were three related sub-syndromes of flat affect, alogia and social dysfunctions. Hallucinations and delusions did not form a homogeneous group of symptoms. Paranoia emerged as a distinct syndrome, and the remaining symptoms could be subdivided into hallucinations, grandiose delusions, and 'loss of boundary' delusions (e.g., thought broadcasting, mind reading). These syndromes, with the exception of loss of boundary delusions, which consisted of SAPS delusions alone, correspond to syndromes of psychosis identified by Lorr and his colleagues thirty years ago. It is concluded that the currently popular 'three syndrome' model does not adequately represent the diversity of psychotic symptoms.

Adult↗