Biomedical subjects

J C Overholser

Publications and source records attributed to J C Overholser.

At least 19 recordsLinked to original sources

PubMed2005

Recovery from major depression: the role of support from family, friends, and spiritual beliefs.

OBJECTIVE: Many of the risk factors for major depression are not amenable to change. The present study was designed to identify factors associated with recovery from depression that could be targets for clinical intervention. METHOD: Sixty-two psychiatric in-patients who met diagnostic criteria for major depression were interviewed while hospitalized and re-interviewed 3 months after discharge. Analyses examined the relationship between depression and three sources of emotional support: family, friends, and spiritual beliefs. RESULTS: Depression severity at baseline was the most consistent predictor of depression severity and diagnosis at follow-up. Patients who had recovered from depression by the time of the follow-up assessment reported higher perceived emotional support from family and friends at baseline. Support from friends, support from family and a composite of emotional support were significant predictors of depression beyond the effects of initial depression severity. CONCLUSION: Aspects of emotional support were significantly associated with depression outcome.

Adult↗

PubMed2004

Low nNOS protein in the locus coeruleus in major depression.

Disruptions of glutamatergic and noradrenergic signaling have been postulated to occur in depressive disorders. Glutamate provides excitatory input to the noradrenergic locus coeruleus (LC). In this study, the location of immunoreactivity against neuronal nitric oxide synthase (nNOS), an intracellular mediator of glutamate receptor activation, was examined in the normal human LC, and potential changes in nNOS immunoreactivity that might occur in major depression were evaluated. Tissue containing LC, and a non-limbic, LC projection area (cerebellum) was obtained from 11 to 12 matched pairs of subjects with major depression and control subjects lacking major psychiatric diagnoses. In the LC region, nNOS immunoreactivity was found in large neuromelanin-containing neurons, small neurons lacking neuromelanin, and glial cells. Levels of nNOS immunoreactivity were significantly lower in the LC (- 44%, p < 0.05), but not in the cerebellum, when comparing depressed with control subjects. nNOS levels were positively correlated with brain pH values in depressed, but not control, subjects in both brain regions. Low levels of nNOS in the LC may reflect altered excitatory input to this nucleus in major depression. However, pH appears to effect preservation of nNOS immunoreactivity in subjects with depression. This factor may contribute, in part, to low levels of nNOS in depression.

Adult↗

PubMed2001

Effects of long-term cigarette smoking on the human locus coeruleus.

BACKGROUND: It has been hypothesized that cigarette smoking among subjects with major depression is a form of self-medication. To explore a possible biological basis for this hypothesis, noradrenergic proteins in the locus coeruleus (LC) were measured in long-term cigarette smokers and in nonsmokers. The LC was studied because elevated amounts of alpha2-adrenoceptors and tyrosine hydroxylase have been observed postmortem in the LCs of subjects with major depression or who commit suicide, and because long-term administration of antidepressant drugs to rats down-regulates these proteins in the LC. METHODS: Postmortem LCs were obtained from long-term cigarette smokers (n=7) and from nonsmokers (n = 9), all of whom lacked diagnoses of major depression. Amounts of tyrosine hydroxylase immunoreactivity and radioligand binding to the norepinephrine transporter, monoamine oxidase A, and alpha2-adrenoceptors were measured. RESULTS: Amounts of tyrosine hydroxylase immunoreactivity and radioligand binding to alpha2-adrenoceptors were significantly lower (approximately 60% and 40%, respectively) along the axis of the LCs of long-term smokers compared with nonsmokers. Smoking had no statistically significant effects on binding to monoamine oxidase A or to the norepinephrine transporter. CONCLUSION: This is the first demonstration that cigarette smoking affects noradrenergic proteins in the LC. The direction of these changes is opposite to that observed when comparing subjects who have major depression with normal controls and the same as that produced by long-term antidepressant treatment in animals. If the present observations reflect long-term effects of smoking on premortem noradrenergic biochemistry, smoking-induced changes in LC biochemistry may strengthen the smoking habit among subjects with major depression.

Antidepressive Agents↗

PubMed2001

RNA editing of the human serotonin 5-HT2C receptor. alterations in suicide and implications for serotonergic pharmacotherapy.

RNA encoding the human serotonin 5-HT2C receptor (5-HT(2C)R) undergoes adenosine-to-inosine RNA editing events at five positions, resulting in an alteration of amino acids in the second intracellular loop. Several edited 5-HT(2C)Rs possess a reduced G-protein coupling efficiency compared to the completely non-edited isoform. The current studies show that the efficacy of the hallucinogenic drug lysergic acid diethylamide and of antipsychotic drugs is regulated by RNA editing, suggesting that alterations in editing efficiencies or patterns might result in the generation of a 5-HT(2C)R population differentially responsive to serotonergic drugs. An examination of the efficiencies of RNA editing of the 5-HT(2C)R in prefrontal cortex of control individuals vs. subjects diagnosed with schizophrenia or major depressive disorder revealed no significant differences in RNA editing among the three populations. However, subjects who had committed suicide (regardless of diagnosis) exhibited a statistically significant elevation of editing at the A-site, which is predicted to change the amino acid sequence in the second intracellular loop of the 5-HT(2C)R. These findings suggest that alterations in RNA editing may contribute to or complicate therapy in certain psychiatric disorders.

Adult↗

PubMed2001

Assessment of mode of anger expression in adolescent psychiatric inpatients.

Anger can play an important role in depression and suicide risk among adolescents. The present study evaluated internalized and externalized anger in 92 adolescent psychiatric inpatients. Results indicated that adolescents who internalized their anger were more likely to be depressed and to experience feelings of hopelessness. In addition, adolescents who internalized their anger made more serious suicide attempts than did those who externalized their anger. In contrast, adolescents who externalized their anger were more likely to have alcohol-related problems. Thus, different modes of anger expression appear to be related to different manifestations of psychopathology. It was concluded that assessment of mode of anger expression in adolescents may enhance our understanding of suicide and its risk factors.

Adolescent↗

PubMed2000

Glial fibrillary acidic protein immunoreactivity in the prefrontal cortex distinguishes younger from older adults in major depressive disorder.

BACKGROUND: Recent postmortem studies in major depressive disorder (MDD) provide evidence for a reduction in the packing density and number of glial cells in different regions of the prefrontal cortex; however, the specific types of glia involved in those morphologic changes are unknown. METHODS: The territory occupied by the astroglial marker glial fibrillary acidic protein (GFAP) was measured as an areal fraction in cortical layers III, IV, and V in sections from the dorsolateral prefrontal cortex (dlPFC) of MDD and control subjects. In addition, the packing density of GFAP-immunoreactive somata was measured by a direct three-dimensional cell counting method. RESULTS: The mean areal fraction and packing density of GFAP-immunoreactive astrocytes in the dlPFC of MDD subjects were not significantly different from those in control subjects; however, in MDD there was a significant strong positive correlation between age and GFAP immunoreactivity. When the MDD group was divided into younger (30-45 years old) and older (46-86) adults, in the five younger MDD adults, areal fraction and packing density were smaller than the smallest values of the control subjects. In contrast, among older MDD subjects these parameters tended to be greater than in the older control subjects. CONCLUSIONS: The present results suggest that the GFAP-immunoreactive astroglia is differentially involved in the pathology of MDD in younger compared with older adults.

Adult↗

PubMed2000

Suicidal ideation in adolescent psychiatric inpatients as associated with depression and attachment relationships.

Examined suicidal ideation in adolescent psychiatric inpatients as associated with depressive symptoms and attachment to mother, father, and peers. Fifty-nine adolescent psychiatric inpatients (25 male, 34 female) completed self-report measures of suicidal ideation, depressive symptoms, and attachment. Attachment to mother accounted for significant variation in levels of depressive symptoms and suicidal ideation. In addition, attachment to peers accounted for significant variation in suicidal ideation and girls' (but not boys') depressive symptoms. However, after adjusting for depressive symptoms, attachment variables failed to contribute additional variance in suicidal ideation. Self-reported depressive symptomatology remained the strongest predictor of suicidal ideation, regardless of its order in the regression analyses. Prevention and treatment efforts may focus on mother-adolescent attachment and peer attachment (particularly in girls) to reduce risk for depression and suicidal ideation.

Adolescent↗

PubMed2000

Risk of future suicide attempts in adolescent psychiatric inpatients at 18-month follow-up.

This study investigated potential predictors of suicidal behavior in adolescents during an 18-month follow-up period. Subjects included 60 adolescent psychiatric inpatients initially assessed in a private psychiatric hospital. Follow-up suicidality was most strongly predicted by high intake levels of hopelessness, and an increase in or persistent problems with depression during follow-up. Some family functioning variables measured at intake were predictive of suicidal behavior at the univariate level but did not add to the predictive ability of individual functioning variables. A mediational model was proposed in which the impact of family functioning on adolescent suicidality is mediated by its impact on individual functioning.

Adolescent↗

PubMed1999

Quantitative distribution of monoamine oxidase A in brainstem monoamine nuclei is normal in major depression.

An abnormal expression of noradrenergic proteins (e.g., tyrosine hydroxylase, norepinephrine transporters) in the locus coeruleus has recently been demonstrated in subjects with major depression and/or victims of suicide. Monoamine oxidase A (MAO-A) is a key enzyme in the catabolism of biogenic amines and is expressed in brain noradrenergic neurons. In this study, the binding of [3H]Ro41-1049 to MAO-A was measured by quantitative autoradiography at multiple levels along the rostral-caudal axis of the noradrenergic locus coeruleus from subjects with major depression and age- and postmortem interval-matched control subjects who were psychiatrically normal. [3H]Ro41-1049 binding to MAO-A was unevenly distributed along the axis of the locus coeruleus, paralleling an uneven number of neuromelanin-containing (noradrenergic) neurons throughout the nucleus. Accordingly, there was a significant correlation between the number of neuromelanin-containing neurons per section and the specific binding of [3H]Ro41-1049 at any particular level of the locus coeruleus in control subjects (r(2)=0.25; p<0.001) and in subjects with major depression (r(2)=0.14; p<0. 001). Moderate levels of [3H]Ro41-1049 binding were observed in regions surrounding the locus coeruleus, including the central gray and the dorsal and median raphe nuclei. No significant differences in [3H]Ro41-1049 binding to MAO-A were observed at any level of the locus coeruleus, or raphe nuclei, comparing subjects with major depression to psychiatrically normal control subjects. These findings demonstrate that the pathophysiology of major depression is not likely to involve abnormalities in MAO-A.

Adult↗

PubMed1999

Elevated levels of tyrosine hydroxylase in the locus coeruleus in major depression.

BACKGROUND: Levels of tyrosine hydroxylase (TH) are regulated in the noradrenergic locus coeruleus (LC) in response to changes in the activity of LC neurons and in response to changes in brain levels of norepinephrine. To study the potential role of central noradrenergic neurons in the pathobiology of major depression, TH protein was measured in the LC from postmortem brains of 13 subjects with a diagnosis of major depression and 13 age-matched control subjects having no Axis I psychiatric diagnosis. Most of the major depressive subjects died as a result of suicide. METHODS: Protein from sections cut through multiple rostro-caudal levels of LC was transferred to Immobilon-P membrane, immunoblotted for TH, and quantified autoradiographically. RESULTS: The distribution of TH-immunoreactivity (TH-ir) along the rostro-caudal axis of the LC was uneven and was paralleled by a similar uneven distribution of neuromelanin-containing cells in both major depressive and psychiatrically normal control subjects. Amounts of TH-ir in the rostral, middle and caudal levels of the LC from major depressive subjects were significantly higher than that of matched control subjects. There were no significant differences in the number of noradrenergic cells at any particular level of the LC comparing major depressive subjects to control subjects. CONCLUSIONS: Elevated expression of TH in the LC in major depression implies a premortem overactivity of these neurons, or a deficiency of the cognate transmitter, norepinephrine.

Adult↗

PubMed1999

Morphometric evidence for neuronal and glial prefrontal cell pathology in major depression.

BACKGROUND: This report provides histopathological evidence to support prior neuroimaging findings of decreased volume and altered metabolism in the frontal cortex in major depressive disorder. METHODS: Computer-assisted three-dimensional cell counting was used to reveal abnormal cytoarchitecture in left rostral and caudal orbitofrontal and dorsolateral prefrontal cortical regions in subjects with major depression as compared to psychiatrically normal controls. RESULTS: Depressed subjects had decreases in cortical thickness, neuronal sizes, and neuronal and glial densities in the upper (II-IV) cortical layers of the rostral orbitofrontal region. In the caudal orbitofrontal cortex in depressed subjects, there were prominent reductions in glial densities in the lower (V-VI) cortical layers that were accompanied by small but significant decreases in neuronal sizes. In the dorsolateral prefrontal cortex of depressed subjects marked reductions in the density and size of neurons and glial cells were found in both supra- and infragranular layers. CONCLUSIONS: These results reveal that major depression can be distinguished by specific histopathology of both neurons and glial cells in the prefrontal cortex. Our data will contribute to the interpretation of neuroimaging findings and identification of dysfunctional neuronal circuits in major depression.

Adult↗

PubMed1999

Brain noradrenergic receptors in major depression and schizophrenia.

The binding of [125I]p-iodoclonidine to alpha-2, and/or [125I]iodopindolol to beta-1 and beta-2 adrenoceptors was measured in right prefrontal cortex (Brodmann's area 10) and right hippocampus from subjects with DSM-III-R diagnoses of major depression (n = 15) or schizophrenia (n = 8) as well as from control subjects (n = 20). No significant differences between study groups were observed in binding to alpha-2 adrenoceptors in any of the six layers of prefrontal cortex or in any of the hippocampal fields. Likewise, there were no significant differences in beta-1 or beta-2 adrenoceptor binding in any of the hippocampal fields between control and major depressive subjects. In contrast, binding to beta-1 adrenoceptors, but not beta-2 adrenoceptors, was significantly lower (-13 to -27%) in most hippocampal fields of schizophrenic subjects as compared to control subjects or to major depressives. Alterations in beta-1 adrenoceptor binding in the hippocampus of schizophrenics provide further evidence for a role of central noradrenergic neurons in the neurochemical pathology of schizophrenia.

Adrenergic alpha-Agonists↗

PubMed1999

Assessing varying degrees of lethality in depressed adolescent suicide attempters.

OBJECTIVE: Understanding the lethality of suicide attempts and its relation to other psychological variables may improve clinical judgement with regard to suicide risk. METHOD: The lethality of suicidal behaviour was examined in 60 hospitalized adolescent in-patients who had recently attempted suicide. Subjects were divided into non-lethal, low-lethal and high-lethal groups based on the qualities of their suicidal acts. RESULTS: The groups did not differ in terms of hopelessness, depression, substance abuse or self-esteem. Moreover, they did not differ significantly in diagnoses of major depression, adjustment disorder, substance abuse and bipolar disorder. The group of high-lethal attempters was the only group with several individuals diagnosed with a major depressive episode and comorbid attention deficit disorder. The high-lethal group also reported the strongest desire to end their lives. CONCLUSION: Based on lethality of suicide attempts, adolescent suicide attempters can be differentiated in terms of the wish to die as well as some instances of diagnostic comorbidity. However, they may not be differentiated in terms of severity of depression or hopelessness, demographic variables and other aspects of suicidal behaviour.

Adolescent↗

PubMed1999

Depression, hopelessness, and self-esteem: accounting for suicidality in adolescent psychiatric inpatients.

The present study was designed to examine depression, hopelessness, and self-esteem as related to suicidal behavior in three groups of depressed adolescent psychiatric inpatients. Depressed adolescents who had never attempted suicide were compared to depressed adolescents who had attempted suicide once and to depressed adolescents who had attempted suicide on several different occasions. Results showed that suicidal adolescents experienced significantly greater depression and hopelessness than did the nonsuicidal adolescents. However, all three groups of depressed adolescents reported similar low levels of self-esteem. Measures of depression and hopelessness were useful in classifying the adolescents based on their suicidal behavior. Results suggest that the treatment of suicidal adolescents could benefit from strategies that focus on reducing feelings of depression and hopelessness.

Adolescent↗

PubMed1998

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↗

PubMed1997

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↗

PubMed1997

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↗

PubMed1997

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↗