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Biomedical subjects

J C Overholser

Publications and source records attributed to J C Overholser.

At least 19 recordsLinked to original sources

Selective increases in phosphoinositide signaling activity and G protein levels in postmortem brain from subjects with schizophrenia or alcohol dependence.

Comparisons of the activity of the G protein-mediated phosphoinositide signal transduction system and of G protein levels were made in two regions of frontal cortex from eight schizophrenic, alcohol-dependent, and control subjects. G protein-mediated phosphoinositide hydrolysis was measured by stimulating cortical membranes incubated with [3H]phosphatidylinositol with 0.3-10 microM guanosine 5'-O-(3-thio)triphosphate (GTPgammaS). In frontal cortex areas 8/9, GTPgammaS-induced phosphoinositide hydrolysis was 50% greater in schizophrenic than control or alcohol-dependent subjects, whereas there were no differences among these groups of subjects in the response to GTPgammaS in frontal cortex area 10. Agonists for dopaminergic, cholinergic, purinergic, serotonergic, histaminergic, and glutamatergic receptors coupled to the phosphoinositide signaling system increased [3H]phosphatidylinositol hydrolysis in a GTPgammaS-dependent manner. Responses to most agonists were similar in all three subject groups in both cortical regions, with the largest difference being a 40% greater response to dopaminergic receptor stimulation in frontal cortex 8/9 from schizophrenic subjects. Measurements of the levels of phospholipase C-beta, and of alpha-subunits of Gq, Go, Gi1, Gi2, and Gs, made by immunoblot analyses revealed no differences among the groups of subjects except for increased G alpha(o) in schizophrenic subjects and increased G alpha(o) and G alpha(i1) in alcohol-dependent subjects. These results demonstrate that schizophrenia is associated with increased activity of the phosphoinositide signal transduction system and increased levels of G alpha(o), whereas the phosphoinositide system was unaltered in alcohol dependence, but G alpha(o) and G alpha(i1) were increased.

Adult

Training issues in cognitive-behavioral psychotherapy.

Because of changes in the health-care system that tend to emphasize short-term treatment, the number of graduate students and psychotherapists interested in learning cognitive-behavioral techniques is increasing. The present study examines how pre-existing biases toward cognitive-behavioral therapy may affect acquisition of knowledge, attitude change, and use of cognitive-behavioral techniques over a nine-month practicum. Forty graduate students were classified by their theoretical orientation: cognitive-behavioral, not cognitive-behavioral, and undecided. Results indicated that all students gained significant amounts of knowledge, had greater positive attitudes about cognitive-behavioral therapy, and used more cognitive and behavioral techniques at the end of the practicum than at the beginning. These findings suggest that pre-existing theoretical orientations may not significantly affect learning of cognitive-behavioral techniques.

Adult

Serotonin receptors in suicide victims with major depression.

Serotonin1A (5-HT1A) and serotonin2A (5-HT2A) receptors in the brain have been implicated in the pathophysiology of suicide. Brain samples were collected at autopsy from suicide victims with a current episode of major depression and matched comparison subjects who died of natural or accidental causes. Retrospective psychiatric assessments were collected from knowledgeable informants for all suicide victims and most of the comparison subjects. Psychiatric diagnoses were determined according to DSM-III-R criteria. Any subjects with current psychoactive substance use disorders were excluded. Quantitative receptor autoradiography was used in serial sections of the right prefrontal cortex (area 10) and hippocampus to measure the binding of [3H]8-hydroxy-2-(di-n-propyl)-aminotetralin ([3H]8-OH-DPAT) to 5-HT1A receptors and [3H]ketanserin to 5-HT2A receptors. Analysis of covariance was used to compare control subjects and suicide victims with major depression. The age of subjects, the time from death to freezing the tissue (postmortem interval), and the storage time of tissues in the freezer were used as covariates in the analyses. There were no significant differences between suicide victims with major depression and comparison subjects in 5-HT1A or 5-HT2A receptors in area 10 of the right prefrontal cortex or the hippocampus. The current results suggest that the number of 5-HT1A and 5-HT2A receptors in the right prefrontal cortex (area 10) or hippocampus are not different in suicide victims with major depression.

Adult

Emotional distress and substance abuse as risk factors for suicide attempts.

BACKGROUND: Both depression and hopelessness have been found to be closely related to suicide risk among adolescents and adults. Substance abuse has also been found to play a role in the suicide process with adults, but it is still unclear how much substance abuse influences suicide in adolescents. METHOD: The present study examined the relationship between substance abuse, emotional distress, and suicidal intent among 115 adolescent psychiatric inpatients who had attempted suicide. RESULTS: Measures of emotional distress, as well as the measures of substance abuse, were significantly intercorrelated. Correlations across domains (emotional distress versus substance abuse), however, varied by gender. Among adolescent females, both depression and hopelessness were significantly related to suicidal intent, whereas among adolescent males, only depression was related to suicidal intent. Also, alcohol abuse was significantly related to depression and hopelessness in adolescent males. CONCLUSIONS: Hopelessness may not be as useful an indicator of suicide risk among adolescent males as it is with adolescent females. Intervention and prevention programs designed for adolescent females should identify and address feelings of depression and hopelessness. New intervention and prevention programs may need to be developed for adolescent males.

Adolescent

Alterations in phosphoinositide signaling and G-protein levels in depressed suicide brain.

The function of the phosphoinositide signal transduction system and the levels of heterotrimeric G-protein alpha-subunits were examined in postmortem prefrontal cortex regions (8/9) and region (10) from suicide victims with major depression and matched control subjects without psychiatric illness. The hydrolysis of [3H]phosphatidylinositol (PI) stimulated by phospholipase C, GTP-gamma-S, NaF, and neurotransmitter receptor agonists was measured in membrane preparations from both groups. Phospholipase C-beta activity was similar in depressed suicide and control subjects in the two regions of prefrontal cortex. In prefrontal cortex (10), but not in (8/9), the GTP-gamma-S concentration-dependent stimulation of [3H]PI hydrolysis was significantly lower (30%) in the depressed suicide group compared to the control group. Receptor-coupled, G-protein-mediated [3H]PI hydrolysis induced with carbachol, histamine, trans-1-aminocyclopentyl-1, 3-dicarboxylic acid (ACPD, a glutamatergic metabotropic receptor agonist), serotonin, or 2-methylthio-adenosine triphosphate (2mATP, a purinergic receptor agonist) in the presence of GTP-gamma-S stimulated equivalent responses in the two groups of subjects in each brain region. In prefrontal cortex (10) there was a 68% increase in the level of the 45 kDa subtype of G alpha s and in prefrontal cortex (8/9) there was a significant decrease (21%) in the level of G alpha i2 in the depressed suicide group compared to the control group. Levels of other heterotrimeric G-protein alpha-subunits (G alpha q/11, G alpha i1, and G alpha o) were not different in depressed suicide and control subjects in either brain region. Moreover, there were no differences in the levels of phospholipase C-beta or protein kinase C-alpha in the two groups of subjects in either brain region examined. These results demonstrate that in the prefrontal cortex of suicide victims with major depression compared to normal control subjects there is a region-specific alteration of G-protein-induced activation of the phosphoinositide signal transduction system and in the levels of G-protein alpha-subunits involved in cyclic AMP synthesis. These findings provide direct evidence in human brain that these two important signal transduction systems are altered in suicide subjects with major depression.

Adult

Serotonin1A receptors are increased in postmortem prefrontal cortex in schizophrenia.

Serotonin-5-HT1A receptors were measured with [3H]8-hydroxy-2-(di-n-propyl)aminotetralin ([3H]8-OH-DPAT) in postmortem prefrontal cortex of 12 pairs of subjects with schizophrenia and age-matched control subjects. The saturation binding isotherms of [3H]8-OH-DPAT revealed high- and low-affinity binding sites. The density (Bmax) of the high-affinity sites was significantly elevated by an average of 79% in subjects with schizophrenia. The dissociation constant (Kd) of the high-affinity sites in subjects with schizophrenia was not significantly different from the control subjects. These results provide further evidence for a role of the serotonergic system in the pathophysiology of schizophrenia.

8-Hydroxy-2-(di-n-propylamino)tetralin

The dependent personality and interpersonal problems.

At the core of the dependent personality disorder lies an excessive reliance on other people for support, direction, and nurturance. However, because of their interpersonal style, many patients high in dependency have difficulties establishing and maintaining close interpersonal relationships. The present study examined interpersonal problems related to the dependent personality disorder. The relationships between dependency and interpersonal problems were examined in 43 adult psychiatric inpatients and 66 nonpatient adults. All subjects were assessed for social functioning in terms of social behaviors typically displayed, density of their social networks, and subjective feelings of loneliness. Using correlations and multiple regression analyses, results showed that dependency was closely related to social behavior and quality of social networks for both psychiatric inpatients and nonpatient controls. Pearson correlations showed the dependent personality style was related to negative and disruptive interpersonal behaviors. Also, measures of social functioning were related to feelings of loneliness and depression. Finally, interpersonal dependency was strongly related to both depressive symptoms and depressive attitudes, especially in the psychiatric inpatients. The present findings demonstrate the importance of interpersonal dependency as related to interpersonal problems.

Adult

Depression following a spinal cord injury.

OBJECT: Depression is a common problem following a spinal cord injury (SCI) and can greatly interfere with the rehabilitation process because of reduced energy, negative expectations, and social withdrawal. Understanding various factors which influence a vulnerability to depression may improve the diagnosis and treatment of depressive disorders and can improve rehabilitation outcome. METHOD: A thorough literature search was conducted using Medline, PsychLit, Pyschinfo, and Social Science Citation Index to identify relevant articles published between 1967 and 1995. RESULTS: A diathesis-stress model is proposed to explain the increased risk of depressive symptoms after a SCI. Biological changes associated with SCI and pre-existing cognitive biases may influence the individual's vulnerability to stressful life events following the injury. The nature and frequency of stressful life events following the injury can tax the individual's coping resources. Furthermore, the perceived quality of social support and the severity of conflict within the family can influence the individual's adaptation. CONCLUSIONS: Social support and recent stressors should be assessed to identify patients at high risk for depression. Patients are less likely to become depressed if their independence is fostered and they are encouraged to develop new sources of self-esteem. Relatives can be counseled to help maintain supportive relationships within the family.

Adaptation, Psychological

Dopamine D4 receptors and effects of guanine nucleotides on [3H]raclopride binding in postmortem caudate nucleus of subjects with schizophrenia or major depression.

The densities of dopamine-D4 receptors were determined in postmortem samples of caudate nucleus from patients with schizophrenia (n = 9) and age-matched controls (n = 10). D4 receptor binding was defined as the difference between binding sites labeled by [3H]YM-09151-2 (D2 + D3 + D4 receptors) and those by [3H]raclopride, in the presence of 5'-guanylylimidodiphosphate (Gpp(NH)p) (D2 + D3 receptors). D4 receptor binding was measurable in all the subjects with schizophrenia (mean = 3.8 pmol/g tissue) but only in 3/10 controls. To determine the specificity of these findings for schizophrenia, D4 receptor binding was also measured in the caudate nucleus of suicide victims with major depression (n = 6) and age-matched controls (n = 6). A small amount of D4 binding was noted in some of the controls + depressed subjects and there was no significant difference between controls and patients with major depression. The addition of 200 microM Gpp(NH)p to the assay significantly increased the amount of specific binding of [3H]raclopride in control tissues, but not in tissues from subjects with schizophrenia, suggesting an abnormality in the G-protein component coupled to the D2 receptor. [3H]Raclopride binding was also significantly increased by Gpp(NH)p in subjects with major depression. These results confirm a previous report of Seeman et al. (1993) and suggest that measurable D4 receptor binding in the caudate nucleus is more frequent in patients with schizophrenia as compared with normal controls and subjects with major depression and that guanine nucleotides do not enhance [3H]raclopride binding in schizophrenia.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Neuropeptide Y in frontal cortex is not altered in major depression.

Previously, we reported a modest but significant reduction in the concentration of neuropeptide Y in frontal cortices from victims of suicide relative to age-matched natural or accidental death control subjects. The reduction in neuropeptide Y appeared to be greatest in a subgroup of victims of suicide for which there was indirect evidence of histories of depression. We pursued these initial findings in the present study by measuring neuropeptide Y concentrations in frontal cortices from natural or accidental death control subjects and from suicide victims in whom a firm diagnosis of major depression was established by psychiatric autopsy. Because several subjects with major depression had a comorbid diagnosis of alcoholism, a group of victims of suicide that had an Axis I diagnosis of alcohol dependence was also studied. No significant differences in neuropeptide Y concentrations were observed between control subjects and victims of suicide with major depression or victims of suicide with alcohol dependence. These findings do not support a role for neuropeptide Y in major depression.

Adult

Self-esteem deficits and suicidal tendencies among adolescents.

OBJECTIVE: Self-esteem can play an important role in suicidal tendencies among adolescents. The present study was designed to examine the relationship between self-esteem deficits and suicidal tendencies in 254 adolescent psychiatric inpatients and 288 high school students. METHOD: The direct relationship between self-esteem and suicidal tendencies was examined by assessing suicidal ideation and history of suicide attempts. An indirect relationship between self-esteem and suicidality was examined by assessing depression and hopelessness. RESULTS: Differences were found across gender and hospitalization status, with males reporting higher self-esteem than females and high school students scoring higher in self-esteem than psychiatric inpatients. However, correlations among variables remained similar across gender and hospitalization status. Thus, low self-esteem was related to higher levels of depression, hopelessness, suicidal ideation, and an increased likelihood of having previously attempted suicide. Furthermore, self-esteem added to the understanding of suicidal ideation beyond what could be explained by depression and hopelessness. CONCLUSIONS: Low self-esteem was closely related to feelings of depression, hopelessness, and suicidal tendencies. Assessment of adolescents should include an evaluation of self-esteem, and therapy should attempt to address any self-esteem deficits.

Adolescent

Perceived family functioning and adolescent suicidal behavior.

OBJECTIVE: Family problems increase the risk of adolescent suicidal behavior, but the specific dimensions of family functioning related to adolescent suicidal ideation and suicide attempts have not been identified clearly. This study examined the relationship between family functioning and adolescent suicidal ideation and suicide attempts. Participating adolescents included psychiatric inpatients who had attempted suicide (n = 35), high school students reporting suicidal ideation (n = 33), nonsuicidal psychiatric inpatients (n = 29), and nonsuicidal high school students (n = 37). METHOD: The Family Assessment Measure was used to assess adolescents' perceptions of family functioning on two levels: (1) the family system and (2) parent-adolescent dyadic relationships. RESULTS: The suicidal psychiatric inpatients and the suicidal high school students did not differ in their perceptions of family functioning and mother-adolescent relationships. However, both suicide groups reported more distress and family dysfunction than did the nonsuicidal high school students. Perceived family functioning and mother-adolescent relationships were significantly correlated with levels of depression, hopelessness, and self-esteem. CONCLUSIONS: Family functioning is important to consider when assessing and treating adolescents for suicidal behavior.

Adolescent

Stressful life events associated with adolescent suicide attempts.

This study was designed to examine the types of stressful events that are related to adolescent suicidal behaviour. Adolescent inpatients who attempted suicide and a control group of high school students were compared on various types of stressors. The stressors were categorized according to their type (for example, discrete events versus chronic strains) and source (for example, family or friends). Compared to high school controls, adolescents who attempted suicide reported elevated levels of major negative events and exit events. Both chronic strains and discrete stressors were related to an increased severity of depression and suicidal ideation. The results support the notion that increased stress is related to adolescent suicidal behaviour. Different approaches to categorizing stress may improve the understanding of the relationship between stressful life events and suicide. Also, sex differences may influence the relationship between life stress and suicidal feelings.

Adolescent

Emotional distress in adolescent psychiatric inpatients: direct and indirect measures.

This study examined whether adolescent male psychiatric inpatients were less likely than comparable female inpatients to communicate their feelings on direct measures of emotional distress. Ninety-one adolescent psychiatric inpatients were assessed using the Rorschach, the Minnesota Multiphasic Personality Inventory, and other measures of emotional distress. In general, male and female subjects reported highly similar levels and patterns of distress whether direct or indirect measures were used. Although the direct measures showed evidence of convergent validity, the indirect measures were largely uncorrelated with each other and with the direct measures. These results suggest that the assessment of emotional distress in both male and female adolescent inpatients is best facilitated by the use of direct measures.

Adolescent

Sex differences, sex roles, and projection on the TAT: matching stimulus to examinee gender.

We examined the assumption that on the Thematic Apperception Test (TAT) examinees identify more with stimulus characters of the same sex as themselves and therefore produce more projective material when tested with these gender matched cards. Repeated measures analyses of variance and t tests showed no increase in projection as a result of matching gender or sex role of subject to card stimulus. Results do not support the clinical utility of the separate male and female sets of TAT cards.

Adult

Diagnostic validity of the passive-aggressive personality disorder: suggestions for reform.

Numerous problems have plagued the diagnosis of the passive-aggressive (P-A) personality disorder. Based on criteria established to evaluate the functional utility of diagnostic categories, the P-A personality disorder does not appear to be an adequate psychiatric diagnosis. However, the concept of passive-aggressiveness may be retained as a useful psychiatric construct when viewed from a dimensional rather than a categorical perspective. A model is presented that describes passive-aggressiveness as consisting of five interrelated psychological factors: rigidity, resentment, resistance, reactance, and reversed reinforcement. This interactive model provides a more detailed and richer description of the P-A style than what is captured in the current diagnostic nomenclature. It is hoped that the model's characterization of P-A in concrete and testable terms will facilitate research into the utility of the passive-aggressiveness construct.

Humans

Suicidal behavior and history of substance abuse.

Substance abuse is frequently associated with suicidal behavior. However, it is unclear to what degree substance abuse in a family member is related to suicide. In the present study, personal and family histories of substance abuse were examined in 716 psychiatric emergency room patients. Suicide attempters, suicide ideators, and nonsuicidal controls were compared across demographic, clinical, and substance abuse variables. Results showed that suicidal patients differed from nonsuicidal controls on many of the dependent variables. Suicidal patients were more likely to be depressed and report a history of previous suicidal tendencies. Also, alcohol and drug abuse occurred more frequently in suicidal patients. Furthermore, a family history of alcohol abuse was reported more often by suicidal than nonsuicidal patients. These patterns of substance abuse in suicidal patients were especially prominent among older subjects. Results are discussed in terms of the implications for identifying psychiatric emergency room patients at risk for suicide.

Adolescent

Prompting and fading in the exposure treatment of compulsive checking.

Compulsive checking can be treated effectively through the use of in vivo exposure with response prevention. However, the clinical application of these procedures can become quite complex. The therapist must help teach the client new coping skills for managing anxiety. However, many compulsive clients report a substantial reduction in the urge to check whenever accompanied by another adult. Therefore, the therapist must not be so intrusive as to reduce the impact of the exposure. Treatment procedures used with two clients are described to show how prompting can be useful for facilitating the early stages of exposure and how fading is essential in promoting self-control. Portable electronic communication devices were used to bridge the gap between therapist-assisted and self-controlled exposure sessions. Therapy was successful in reducing the frequency of checking behaviors and the subjective urge to check.

Adaptation, Psychological