Biomedical subjects

J J Mann

Publications and source records attributed to J J Mann.

At least 37 records · Page 2Linked to original sources

PubMed2001

Treating the substance-abusing suicidal patient.

Studies concerning the treatment of substance-abusing suicidal patients are scarce despite the frequent presence of suicidal behavior among this population. Indeed, suicidality (ideation or behavior) is generally an exclusion criterion for participation in treatment studies of subjects with alcohol or drug abuse. Consequently, to date, little is known about the optimal treatment of this population. The first study involving substance-abusing suicidal patients was an open-label trial conducted in the early 1990s. This study involved 12 patients, all of whom demonstrated recent suicidal ideations and had made a lifetime suicide attempt. The results of that open-label study demonstrated significant within-group improvement in both depressive symptoms (including suicidal ideations) and level of drinking. However, substantial residual depressive symptoms and drinking persisted at the end of the trial. Also, because no placebo control group was utilized, the authors of that study could not rule out the possibility that the apparent therapeutic effect from fluoxetine was the result of the placebo effect. To date, only one double-blind, placebo-controlled study of subjects with alcohol or substance abuse has included substantial numbers of suicidal patients. The study involved 51 subjects, of whom 20 (39%) had made a suicide attempt in the current depressive episode, 31 (61%) had made a suicide attempt in their lifetime, and 46 (90%) had reported suicidal ideations in the week before hospitalization. The results of that double-blind, placebo-controlled study suggest that fluoxetine was effective in decreasing but not eliminating both the depressive symptoms (including suicidal ideations) and the level of alcohol consumption among a study group of subjects with comorbid major depressive disorder and alcohol dependence, many of whom displayed suicidal ideations. A secondary data analysis from that study suggested that cigarette smoking is also significantly decreased by fluoxetine, but the magnitude of the decrease is limited and few of these patients totally quit smoking with fluoxetine treatment alone. Another secondary data analysis from that study suggested that marijuana smoking was also significantly decreased in a subgroup of subjects who demonstrated cannabis abuse and that the magnitude of this improvement was robust. A third secondary data analysis from that study suggested that cocaine abuse acts as a predictor of poor outcome for both depressive symptoms (including suicidality) and level of alcohol use in this population. The results of a 1-year naturalistic follow-up study involving the patients from that study suggest that the benefits of fluoxetine in decreasing depressive symptoms and level of drinking persist 1 year after entering the treatment program. To date, no other double-blind, placebo-controlled studies involving substantial numbers of substance-abusing suicidal patients have been reported to either confirm or refute these findings. Further studies are clearly warranted to evaluate the efficacy of various pharmacotherapeutic agents and various psychotherapies in the treatment of substance-abusing suicidal patients.

Adult↗

PubMed2001

Ethnic and sex differences in suicide rates relative to major depression in the United States.

OBJECTIVE: Suicide rates differ between ethnic groups in the United States. Since suicide is commonly associated with a mood disorder, the authors compared suicide rates relative to depression rates in five ethnic groups in the United States. METHOD: Rates of major depression were generated from the Epidemiologic Catchment Area study and the Hispanic Health and Nutrition Epidemiologic Survey. Sociodemographic effects were determined by examining depression rates for respondents who were separated or divorced, earning low incomes, or not working for pay. The survey data were analyzed with age and sex standardization to generate 1-year prevalence rates of major depression. The depression rates of the different ethnic groups were compared and were examined in relation to suicide rates. RESULTS: The 1-year prevalence rates of major depression were 3.6% for whites, 3.5% for blacks, 2.8% for Mexican Americans, 2.5% for Cuban Americans, and 6.9% for Puerto Ricans. Compared to the rate for whites, the rate of depression was significantly higher in Puerto Ricans and significantly lower in Mexican Americans. Relative to the depression rates, the annual suicide rates were higher for males than for females. Mexican American and Puerto Rican males had lower relative suicide rates than white males. CONCLUSIONS: Identifying reasons for differences in suicide rates relative to depression among ethnic groups and between males and females may suggest interventions to reduce suicide rates. Some possibilities are that depression differs in form or severity or that unidentified factors protect against suicide in different subgroups.

Adult↗

PubMed2001

The relationship of childhood abuse to impulsivity and suicidal behavior in adults with major depression.

OBJECTIVE: This study investigated whether a higher frequency of reported childhood trauma would be found in depressed adults with higher levels of trait impulsivity, aggression, and suicidal behavior. METHOD: In 136 depressed adult inpatients, the authors assessed trait impulsivity, aggression history, and number of lifetime suicide attempts as well as the medical lethality and the intent to die associated with the most lethal attempt. These variables were then compared between those with and those without a reported history of childhood physical or sexual abuse. RESULTS: Subjects who reported an abuse history were more likely to have made a suicide attempt and had significantly higher impulsivity and aggression scores than those who did not report an abuse history. Impulsivity and aggression scores were significantly higher in subjects with a history of at least one suicide attempt. A logistic regression analysis revealed that abuse history remained significantly associated with suicide attempt status after adjustment for impulsivity, aggression history, and presence of borderline personality disorder. Among those who attempted suicide, there were no significant differences in severity of suicidal behavior between those with and without a childhood history of abuse. CONCLUSIONS: Abuse in childhood may constitute an environmental risk factor for the development of trait impulsivity and aggression as well as suicide attempts in depressed adults. Alternatively, impulsivity and aggression may be inherited traits underlying both childhood abuse and suicidal behavior in adulthood disorders. Additional research is needed to estimate the relative contributions of heredity and environmental experience to the development of impulsivity, aggression, and suicidal behavior.

Adult↗

PubMed2001

Decreased regional brain metabolism after ect.

OBJECTIVE: The antidepressant action of ECT may be related to its anticonvulsant properties. Positron emission tomography (PET) studies of regional cerebral metabolic rate for glucose were used to test this hypothesis. METHOD: Ten patients with major depression were studied with PET before and approximately 5 days after a course of bilateral ECT. Statistical parametric mapping was used to identify regions of decreased cerebral glucose metabolism. RESULTS: Widespread regions of decreased regional cerebral glucose metabolism were identified after ECT, especially in the frontal and parietal cortex, anterior and posterior cingulate gyrus, and left temporal cortex. A region-of-interest analysis similarly indicated post-ECT reductions in regional cerebral glucose metabolism. CONCLUSIONS: ECT reduces neuronal activity in selected cortical regions, a potential anticonvulsant and antidepressant effect.

Brain↗

PubMed2001

Are suicide attempters who self-mutilate a unique population?

OBJECTIVE: Individuals who mutilate themselves are at greater risk for suicidal behavior. Clinically, however, there is a perception that the suicide attempts of self-mutilators are motivated by the desire for attention rather than by a genuine wish to die. The purpose of this study was to determine differences between suicide attempters with and without a history of self-mutilation. METHOD: The authors examined demographic characteristics, psychopathology, objective and perceived lethality of suicide attempts, and perceptions of their suicidal behavior in 30 suicide attempters with cluster B personality disorders who had a history of self-mutilation and a matched group of 23 suicide attempters with cluster B personality disorders who had no history of self-mutilation. RESULTS: The two groups did not differ in the objective lethality of their attempts, but their perceptions of the attempts differed. Self-mutilators perceived their suicide attempts as less lethal, with a greater likelihood of rescue and with less certainty of death. In addition, suicide attempters with a history of self-mutilation had significantly higher levels of depression, hopelessness, aggression, anxiety, impulsivity, and suicide ideation. They exhibited more behaviors consistent with borderline personality disorder and were more likely to have a history of childhood abuse. Self-mutilators had more persistent suicide ideation, and their pattern for suicide was similar to their pattern for self-mutilation, which was characterized by chronic urges to injure themselves. CONCLUSIONS: Suicide attempters with cluster B personality disorders who have a history of self-mutilation tend to be more depressed, anxious, and impulsive, and they also tend to underestimate the lethality of their suicide attempts. Therefore, clinicians may be unintentionally misled in assessing the suicide risk of self-mutilators as less serious than it is.

Adult↗

PubMed2001

Neuropsychological dysfunction in depressed suicide attempters.

OBJECTIVE: Neuropsychological deficits in the context of psychiatric disease may be associated with suicide risk. In this study, neuropsychological performance was compared among depressed patients with at least one prior suicide attempt of high lethality, depressed patients with low-lethality prior attempts, depressed patients with no prior suicide attempts, and nonpatients. METHOD: Fifty unmedicated patients in a major depressive episode (21 with no history of suicide attempts and 14 and 15 patients with previous attempts of low and high lethality, respectively) and 22 nonpatients were assessed. Groups were comparable in age, education, occupational level, and estimated premorbid intelligence. The neuropsychological battery produced scores within five composite domains: general intellectual functioning (current), motor functioning, attention, memory, and executive functioning. RESULTS: Patients whose prior suicide attempts were of high lethality performed significantly worse than all groups on tests of executive functioning and were the only group to perform significantly worse than nonpatients on tests of general intellectual functioning, attention, and memory. A discriminant function analysis revealed two prominent dimensions in the data: one that discriminated high-lethality suicide attempters from all other groups (primarily associated with performance on tests of executive functioning) and another that discriminated all depressed patient groups from nonpatients (associated with performance on measures of attention and memory). For the patients with high-lethality prior suicide attempts, deficits did not appear to reflect diffuse brain damage from past attempts, since the results of tests commonly affected by diffuse injury were not selectively impaired. CONCLUSIONS: Neuropsychological deficits in depressed patients with high-lethality prior suicide attempts suggest impairment of executive functioning beyond that typically found in major depression. This more extensive neuropsychological impairment in the context of depression may be a risk factor for severe suicide attempts.

Adult↗

PubMed2001

Delusions and suicidality.

OBJECTIVE: Delusions have been considered a risk factor for suicidal behavior. To determine whether specific delusion types are related to suicidal behaviors, the authors compared the clinical characteristics of patients with mood disorders and schizophrenia who did and did not have a history of suicide attempts. METHOD: After admission for inpatient or outpatient psychiatric treatment, 429 patients (ages 14-72 years; 47.1% male; and 73.0% Caucasian) were assessed with a structured clinical interview that generated axis I and II diagnoses. In addition, their psychiatric symptoms, history of suicide attempts, and overall functioning were rated. RESULTS: Data for three diagnostic subgroups (223 patients with major depression, 150 with schizophrenia, and 56 with bipolar disorder) were analyzed separately. Multivariate analyses did not find evidence of a relationship between delusions and history of suicidal ideation or suicide attempts in any of the diagnostic groups. CONCLUSIONS: This study did not find evidence that the presence of delusions distinguished persons with or without a history of suicide attempt.

Adolescent↗

PubMed2001

Identifying and managing suicide risk in bipolar patients.

Bipolar patients have been shown to be at high risk for suicidal behavior. Therefore, identifying potentially suicidal patients is necessary in the treatment of bipolar patients. A stress-diathesis model for suicidal behavior has been proposed to assist clinicians in determining which patients are at risk. In the model, suicidal behavior is the result of the interaction between an individual's threshold for suicidal acts and the stressors that can lead to suicidal behavior. Suicide risk factors can then be categorized as either diathesis-related or stress-related. In a study applying the model of suicidal behavior to bipolar disorder, bipolar patients who attempted suicide had higher levels of suicidal ideation, lifetime aggression, and substance abuse than the comparison group of nonattempters. Attempters had twice the number of major depressive episodes. Once high-risk patients are identified, their suicide risk can be managed through treatments such as prophylactic lithium treatment and other pharmacologic approaches.

Bipolar Disorder↗

PubMed2000

Modulation of amphetamine-induced striatal dopamine release by ketamine in humans: implications for schizophrenia.

BACKGROUND: Recent brain imaging studies have indicated that schizophrenia is associated with increased amphetamine-induced dopamine release in the striatum. It has long been hypothesized that dysregulation of subcortical dopamine systems in schizophrenia might result from a failure of the prefrontal cortex (PFC) to adequately control subcortical dopaminergic function. The activity of midbrain dopaminergic neurons is regulated, in part, by glutamatergic projections from the PFC acting via glutamatergic N-methyl-D-aspartate (NMDA) receptors. The goal of this study was to test the hypothesis that a pharmacologically induced disruption of NMDA transmission leads to an increase in amphetamine-induced dopamine release in humans. METHODS: In eight healthy volunteers, we compared striatal amphetamine-induced (0.25 mg/kg) dopamine release under control conditions and under sustained disruption of NMDA transmission induced by infusion of the noncompetitive NMDA antagonist ketamine (0.2 mg/kg intravenous bolus followed by 0.4 mg/kg/hour intravenous infusion for 4 hours). Amphetamine-induced dopamine release was determined with single photon emission computed tomography, as the reduction in the binding potential (BP) of the radiolabeled D(2) receptor antagonist [(123)I]IBZM. RESULTS: Ketamine significantly enhanced the amphetamine-induced decrease in [(123)I]IBZM BP, from -5.5% +/- 3.5% under control conditions to -12. 8% +/- 8.8% under ketamine pretreatment (repeated-measures analysis of variance, p =.023). CONCLUSIONS: The increase in amphetamine-induced dopamine release induced by ketamine (greater than twofold) was comparable in magnitude to the exaggerated response seen in patients with schizophrenia. These data are consistent with the hypothesis that the alteration of dopamine release revealed by amphetamine challenge in schizophrenia results from a disruption of glutamatergic neuronal systems regulating dopaminergic cell activity.

Adult↗

PubMed2000

In vitro autoradiography of serotonin 5-HT(2A/2C) receptor-activated G protein: guanosine-5'-(gamma-[(35)S]thio)triphosphate binding in rat brain.

Agonist activation of G protein-coupled receptors induces an increase in the binding of guanosine 5'-(gamma-[(35)S]thio)triphosphate ([(35)S]GTPgammaS); this increase in binding has been used as a tool to investigate receptor interaction with the heterotrimer guanine nucleotide-binding regulatory protein (G protein). The present study uses agonist-stimulated [(35)S]GTPgammaS binding to characterize serotonin 5-HT(2A/2C) receptors in rat brain membrane fractions and demonstrate the anatomical localization of the receptors by in vitro autoradiography on slide-mounted sections. The stimulatory effect of the agonist [1-(2,5-dimethoxy-4-iodophenyl)]-2 aminopropane (DOI) is compared to that of serotonin (5-HT). Autoradiography revealed a similar localization of DOI- and 5-HT-stimulated binding of [(35)S]GTPgammaS in distinct areas of prefrontal and parietal cortex, consistent with previously reported 5-HT(2A) receptor distribution. Specific binding was demonstrated in the frontal and parietal cortex, medial prefrontal, and cingular and orbital-insular areas as well as in the hippocampal formation, septal areas, the nucleus accumbens, and the choroid plexus. MDL 100105, a specific 5-HT(2A) antagonist, and ketanserin, an antagonist of 5-HT(2A/2C) receptors, blocked DOI stimulation in all labeled areas, whereas 5-HT stimulation was only partially blocked (70-80%). A small but significant inhibition was observed with the specific antagonist of 5-HT(2C/2B), SB 206553. This autoradiographic technique provides a useful tool for measuring in situ changes in specific receptor-Gq protein coupling in anatomically discrete brain regions, under physiological and pathological conditions.

Amphetamines↗

PubMed2000

Mixed models and multiple comparisons in analysis of human neurochemical maps.

Examination of brain regional neurochemistry in disease states reveals differences among brain regions. Knowing where alterations in brain function are located is crucial to understanding the disease effect. The anatomical distribution of neurotransmitter receptors is now often studied using quantitative autoradiography, but the large number of brain regions involved raises serious problems for statistical analysis of such data. Due to the dependence among the subjects in case control designs, statistical analysis based on a 'mixed model' is useful. Such an analysis is illustrated using a small autoradiographic data set. The Bonferroni method, the method of Holm, and two 'False Discovery Rate'-controlling methods for adjusting P-values for multiple comparisons are compared.

Autoradiography↗

PubMed2000

A regulatory polymorphism of the monoamine oxidase-A gene may be associated with variability in aggression, impulsivity, and central nervous system serotonergic responsivity.

This study presents preliminary evidence of an association between polymorphic variation in the gene for monoamine oxidase-A (MAOA) and interindividual variability in aggressiveness, impulsivity and central nervous system (CNS) serotonergic responsivity. An apparently functional 30-bp VNTR in the promoter region of the X-chromosomal MAOA gene (MAOA-uVNTR), as well as a dinucleotide repeat in intron 2 (MAOA-CAn), was genotyped in a community sample of 110 men. All participants had completed standard interview and questionnaire measures of impulsivity, hostility and lifetime aggression history; in a majority of subjects (n=75), central serotonergic activity was also assessed by neuropsychopharmacologic challenge (prolactin response to fenfluramine hydrochloride). The four repeat variants of the MAOA-uVNTR polymorphism were grouped for analysis (alleles '1+ 4' vs. '2+3') based on prior evidence of enhanced transcriptional activity in MAOA promoter constructs with alleles 2 and 3 (repeats of intermediate length). Men in the 1/4 allele group scored significantly lower on a composite measure of dispositional aggressiveness and impulsivity (P<0.015) and showed more pronounced CNS serotonergic responsivity (P<0.02) than men in the 2/3 allele group. These associations were also significant on comparison of the more prevalent one and three alleles alone (encompassing 93% of subjects). Although in linkage disequilibrium with the MAOA-uVNTR polymorphism, MAOA-CAn repeat length variation did not vary significantly with respect to behavior or fenflluramine challenge in this sample. We conclude that the MAOA-uVNTR regulatory polymorphism may contribute, in part, to individual differences in both CNS serotonergic responsivity and personality traits germane to impulse control and antagonistic behavior.

Adult↗

PubMed2000

Increased baseline occupancy of D2 receptors by dopamine in schizophrenia.

The classical dopamine hypothesis of schizophrenia postulates a hyperactivity of dopaminergic transmission at the D(2) receptor. We measured in vivo occupancy of striatal D(2) receptors by dopamine in 18 untreated patients with schizophrenia and 18 matched controls, by comparing D(2) receptor availability before and during pharmacologically induced acute dopamine depletion. Acute depletion of intrasynaptic dopamine resulted in a larger increase in D(2) receptor availability in patients with schizophrenia (19% +/- 11%) compared with control subjects (9% +/- 7%, P = 0.003). The increased occupancy of D(2) receptors by dopamine occurred both in first-episode neuroleptic-naive patients and in previously treated chronic patients experiencing an episode of illness exacerbation. In addition, elevated synaptic dopamine was predictive of good treatment response of positive symptoms to antipsychotic drugs. This finding provides direct evidence of increased stimulation of D(2) receptors by dopamine in schizophrenia, consistent with increased phasic activity of dopaminergic neurons.

Adult↗

PubMed2000

Hippocampal pathology in schizophrenia: magnetic resonance imaging and spectroscopy studies.

The hippocampus is a site of previously reported structural and functional abnormalities in schizophrenia. We used magnetic resonance imaging (MRI) and proton magnetic resonance spectroscopy (MRS) to measure gray matter volumes, the neuronal marker N-acetylaspartate (NAA), and the combination of glutamate (Glu), glutamine (Gln), and gamma-aminobutyric acid (GABA), designated Glx. Measurements were obtained of the medial temporal lobe, centered on the hippocampus, in 10 male patients with schizophrenia (3 neuroleptic-medicated and 7 medication-free), and 10 matched normal volunteers. MRI volumetric measurements and MRS data obtained with short echo time (TE=20 ms) one-dimensional STEAM chemical shift imaging (CSI) on a GE 1.5 Tesla Signa system were analyzed. A laterality index ¿(L-R)/(L+R) was generated from the ratio of Glx to choline-containing compounds (Cho) to test asymmetry changes. Reliability of the MRS measures was assessed with five test-retest studies of healthy volunteers and showed coefficients of variation (CV) in the range of 36-44% for the MRS ratios and standard deviations (S.D.) of 0.15-0.17 for the laterality indices. The Glx/Cho laterality index showed a relative right-sided excess in this region in the patients (-0.23+/-0.20) compared to the controls (+0.06+/-0.20), which was not confounded by tissue composition or placement variability of the MRS voxels. Hippocampal volume deficit and asymmetry were not significant, and other MRS measures showed no differences between patients and controls. The preliminary finding of a lateralized abnormality in Glx is consistent with postmortem findings of asymmetric neurochemical temporal lobe abnormalities in schizophrenia.

Adult↗

PubMed2000

Nocturnal growth hormone secretion studies in adolescents with or without major depression re-examined: integration of adult clinical follow-up data.

BACKGROUND: Early sleep is associated with an increased secretion of human growth hormone (GH) through muscarinic inhibition of somatostatin, a GH suppressant. A clinical follow-up was performed approximately 1 decade after depressed and psychiatrically "normal" control adolescents, who were now young adults, had undergone baseline serial GH measurements over a 24-hour period on the third night of sleep polysomnography studies. METHODS: The study population consisted of 77 young adults who had received a diagnosis of adolescent major depressive disorder and had participated in the adolescent sleep and neuroendocrine studies. Alternatively, the young adult subjects were assessed as normal adolescent control subjects free of any psychiatric diagnosis. Blood samples had been collected for GH every 20 min during the 24-hour period coinciding with the third consecutive night of sleep electroencephalography. Subjects, now in young adulthood, were relocated and blindly reinterviewed using the Schedule for Affective Disorders and Schizophrenia (lifetime version). The original adolescent nocturnal GH data were analyzed in light of the information obtained regarding clinical course into adulthood. RESULTS: A substantial proportion of the nominally normal control group developed at least one episode of major depression or dysthymia during the follow-up period. "Latent" depressive subjects differed from depression-free control subjects by having exhibited a significantly more rapid increase of adolescent nocturnal GH secretion following sleep onset. Of the subjects who had experienced at least one lifetime major depressive episode during the follow-up, the subgroup who would go on to make suicide attempts secreted significantly greater amounts of GH during the first 4 hours of sleep. Adults with lifetime depression exhibited significantly reduced levels of GH in the 100 min preceding sleep onset during adolescence. CONCLUSIONS: Assignment of subjects based on longitudinal clinical follow-up into adulthood revealed that the sleep-related GH secretion paradigm has predictive value for future depressive episodes and future suicide attempts. Dysfunction of complex sleep-onset mechanisms may be a premorbid marker of depression and suicidal behavior.

Adolescent↗

PubMed2000

The human nucleus of the solitary tract: visceral pathways revealed with an "in vitro" postmortem tracing method.

Visceral relay neurons in the nucleus of the solitary tract (NTS) regulate behavior and autonomic reflex functions. NTS projections have been extensively characterized in animal studies but not in humans. For the first time, NTS fiber trajectories in the human medulla oblongata were revealed with an "in vitro" postmortem tracing method. Local intramedullary pathways were labeled by direct pressure injections of free horseradish peroxidase centered on the medial subnucleus at a level adjacent to true obex. Labeled elements were resolved by peroxidase histochemistry as a dark brown intracellular reaction product. A prominent transtegmental system of axons emerged from the NTS injection sites and entered the intermediate reticular zone, a region corresponding to an autonomic reflex center in other mammals. A medial system of axons arched across the dorsomedial reticular formation toward the dorsal medullary raphe and projected ventrally toward the nucleus gigantocellularis. A small lateral fiber trajectory coursed towards the dorsomedial zone of spinal trigeminal nucleus caudalis. Presumptive terminals appeared as dustings of fine punctate processes within the NTS, dorsomotor nucleus and reticular formation. NTS projections in humans resemble those identified in other mammals including primates. Axonal tracing studies predict that visceral impulses in humans may transmit over evolutionarily conserved pathways involved in autonomic feedback control and stress adaptation.

Adult↗

PubMed2000

Structural abnormalities of subicular dendrites in subjects with schizophrenia and mood disorders: preliminary findings.

BACKGROUND: Postmortem studies of the subiculum from subjects with schizophrenia have detected smaller pyramidal cell bodies and diminished immunoreactivity for the dendritic protein, microtubule-associated protein 2. While these findings suggest that subicular pyramidal cell dendrites may be structurally altered in subjects with schizophrenia, this possibility had not been tested directly. METHODS: Rapid Golgi impregnation of archival brain specimens was used to compare the morphologic characteristics of subicular dendrites in subjects with schizophrenia (n = 13) and mood disorders (n = 6) with subjects without psychiatric disease (n = 8). The specimens were processed and analyzed by physicians blind to diagnosis. The extent of dendritic trees in the subiculum and fusiform gyrus was examined by Sholl analysis. Spine density on apical dendrites of subicular pyramidal cells was determined at a fixed distance from the cell body. RESULTS: Spine density and arborization of subicular apical dendrites were significantly related to diagnostic group. Spine density was significantly lower in the schizophrenia and mood disorder groups than in the nonpsychiatric group. Among the mood disorder cases, diminished spine density was apparently related to a strong family history of major psychiatric diseases. There were no significant effects of diagnostic group on Sholl analysis of nonapical subicular dendrites nor on Sholl analysis of dendrites of neocortical pyramidal cells in the fusiform gyrus. CONCLUSIONS: We have observed an association between schizophrenia and major mood disorders and structural abnormalities of subicular apical dendrites. Further studies are needed to test this association in a larger sample and to evaluate the potential role of family history and of confounding factors, such as medications and chronic institutionalization.

Adult↗

PubMed2000

A serotonin transporter gene promoter polymorphism (5-HTTLPR) and prefrontal cortical binding in major depression and suicide.

BACKGROUND: Major depression and suicide are associated with fewer serotonin transporter (5-HTT) sites. The 5'-flanking promoter region of the 5-HTT gene has a biallelic insertion/deletion (5-HTTLPR). We assayed prefrontal cortical (PFC) 5-HTT binding in major depression and suicide and examine the relationship to the 5-HTTLPR allele. METHODS: Postmortem brain samples from 220 individuals were genotyped for the 5-HTTLPR polymorphism. Binding of 5-HTT was assayed by quantitative autoradiography in the PFC of a subset of subjects (n = 159). Clinical information, including DSM-III-R Axis I diagnoses, was obtained by psychological autopsy and medical chart review. RESULTS: Binding to 5-HTT was lower in the ventral PFC of suicides compared with nonsuicides and was lower throughout the PFC of subjects with a history of major depression. The 5-HTTLPR genotype was associated with major depression but not with suicide or 5-HTT binding. CONCLUSIONS: A diffuse reduction of 5-HTT binding in the PFC of individuals with major depression may reflect a widespread impairment of serotonergic function consistent with the range of psychopathologic features in major depression. The localized reduction in 5-HTT binding in the ventral PFC of suicides may reflect reduced serotonin input to that brain region, underlying the predisposition to act on suicidal thoughts. The 5-HTTLPR genotype was not related to the level of 5-HTT binding and does not explain why 5-HTT binding is lower in major depression or suicide. Arch Gen Psychiatry. 2000;57:729-738

Adult↗