BD Subjects Research Articles

Childhood Clinical Features Preceding the Onset of Bipolar Versus Major Depressive Disorders During Adolescence

Objective: To identify childhood psychopathological features that predict the onset of adolescent Bipolar (BD) versus Unipolar Major Depressive Disorder (UD) during adolescence. Method: We analyzed clinical data from 495 juveniles diagnosed with DSM-5 UD (n = 359), and BD (n = 136), using bivariate analysis and multivariate logistic regression model. Results: BD subjects exhibited earlier onset of any psychiatric feature compared to UD. Antecedents associated with later BD were: oppositional defiant > specific phobias > ADHD > obsessive compulsive (OCD). Antecedents selectively associated with later UD were: social anxiety and separation anxiety. Factors significantly and independently associated with later BD diagnosis were: [a] emotional dysregulation at onset of the mood disorder; [b] first depressive episode with mixed features; [c] antecedent ADHD; [d] antecedent OCD, and [e] antecedent oppositional-defiance. Conclusion: Identifying developmental differences in BD and UD symptoms can aid clinicians in early identification and treatment planning for bipolar disorder in youth.

Choroidal vascularity index and submacular choroidal thickness in patients with Behçet disease assessed with enhanced-depth OCT

ObjectifExaminer les changements qui se produisent dans la choroïde grâce à l'indice de vascularisation choroïdienne (IVC) et à l’épaisseur choroïdienne (EC) en présence de maladie de Behçet (MB) avec ou sans atteinte oculaire. MéthodesOnt été inclus 68 patients présentant une MB oculaire, 40 patients présentant une MB sans atteinte oculaire et 40 sujets témoins en bonne santé. L'EC a été mesurée par tomographie par cohérence optique à l'imagerie à profondeur améliorée (EDI-OCT, pour enhanced-depth imaging optical coherence tomography; EC sous-fovéale à 1000 μm, EC nasale à 1000 μm et EC temporale). L'IVC (%) a été calculé en divisant l'aire luminale par l'aire choroïdienne sous-fovéale totale. RésultatsL'EC moyenne sous-fovéale (297 ± 68 µm), nasale (261 ± 66 µm) et temporale (272 ± 68 µm) dans les yeux présentant une MB oculaire et l'EC moyenne sous-fovéale (286 ± 31 µm), nasale (266 ± 29 µm) et temporale (269 ± 32 µm) dans les yeux présentant une MB sans atteinte oculaire étaient significativement moindres, comparativement aux mêmes zones chez les témoins en bonne santé (333 ± 69, 301 ± 75 et 312 ± 70 µm, respectivement). On a réalisé une autre analyse de sous-groupes (MB oculaire active, MB oculaire non active, MB sans atteinte oculaire et groupe témoin) ainsi que des comparaisons par paires. Or, l'IVC était significativement moins élevé dans les groupes MB oculaire active (64,3 ± 3,1) et MB oculaire non active (64,2 ± 4,5), comparativement au groupe témoin (67,2 ± 3,6; p = 0,026 et p < 0,001, respectivement). On n'a pas observé de différence significative entre le groupe MB sans atteinte oculaire (65,9 ± 3,4) et le groupe témoin (67,2 ± 3,6) au chapitre de l'IVC (p > 0,05). ConclusionsLa baisse de l'IVC en présence de MB oculaire laisse supposer que l'uvéite perturbe le système vasculaire choroïdien et la perfusion sanguine, tandis que l'inflammation générale dans la MB sans atteinte oculaire n'a aucun effet à cet égard. Qui plus est, c'est le caractère chronique de l'uvéite qui a des effets sur la choroïde plutôt que l'activité de la maladie en soi. La mesure de l'EC et de l'IVC représente peut-être un nouveau biomarqueur fiable du pronostic, qui permet d’évaluer le système vasculaire choroïdien et de surveiller la progression de la maladie en présence de MB oculaire grâce à l'EDI-OCT, une modalité d'imagerie non invasive. Cela dit, l'IVC ne semble pas constituer un biomarqueur permettant la surveillance de l'activité de la maladie ou de l'efficacité du traitement.

Peripheral and central levels of kynurenic acid in bipolar disorder subjects and healthy controls

Metabolites of the kynurenine pathway of tryptophan degradation, in particular, the N-Methyl-d-aspartic acid receptor antagonist kynurenic acid (KYNA), are increasingly recognized as primary pathophysiological promoters in several psychiatric diseases. Studies analyzing central KYNA levels from subjects with psychotic disorders have reported increased levels. However, sample sizes are limited and in contrast many larger studies examining this compound in blood from psychotic patients commonly report a decrease. A major question is to what extent peripheral KYNA levels reflect brain KYNA levels under physiological as well as pathophysiological conditions. Here we measured KYNA in plasma from a total of 277 subjects with detailed phenotypic data, including 163 BD subjects and 114 matched healthy controls (HCs), using an HPLC system. Among them, 94 BD subjects and 113 HCs also had CSF KYNA concentrations analyzed. We observe a selective increase of CSF KYNA in BD subjects with previous psychotic episodes although this group did not display altered plasma KYNA levels. In contrast, BD subjects with ongoing depressive symptoms displayed a tendency to decreased plasma KYNA concentrations but unchanged CSF KYNA levels. Sex and age displayed specific effects on KYNA concentrations depending on if measured centrally or in the periphery. These findings implicate brain-specific regulation of KYNA under physiological as well as under pathophysiological conditions and strengthen our previous observation of CSF KYNA as a biomarker in BD. In summary, biomarker and drug discovery studies should include central KYNA measurements for a more reliable estimation of brain KYNA levels.

Antisuicidal Effects in Mood Disorders: Are They Unique to Lithium?

Suicidal behavior is strongly associated with depression in major depressive (MDD) and bipolar (BD) disorders, especially with associated behavioral activation, dysphoria, or agitation. A rare intervention with evidence of suicide risk-reducing as well as mood-stabilizing effects in mood disorder patients is lithium. We reviewed available research evidence on associations of long-term treatment with lithium with risk of suicidal behavior. We meta-analyzed 12 randomized trials in 10 reports (with at least 1 suicide in either treatment arm) including both BD and MDD subjects, with particular attention to comparisons of lithium with placebo or other pharmacological treatments. We also summarized ecological studies on lithium concentration in local drinking water and reported suicide rates. We found substantial reduction of risks of suicide and attempts with long-term lithium treatment, particularly in depressive phases of BD and in MDD. Risk of suicidal behavior was higher in mixed (agitated-dysphoric) states than in manic or hypomanic periods. Risk of suicide fatality, specifically, was lower with lithium than with placebo and probably with mood-altering anticonvulsants or antidepressants. Long-term treatment with lithium has growing evidence of suicide- and attempt-sparing effects, probably greater than with anticonvulsants or antidepressants; antipsychotics remain to be tested adequately. However, the ethical and scientifically adequate design and conduct of trials of treatments aimed at suicide prevention remain challenging and underdeveloped.

Exon Array Biomarkers for the Differential Diagnosis of Schizophrenia and Bipolar Disorder

This study developed potential blood-based biomarker tests for diagnosing and differentiating schizophrenia (SZ), bipolar disorder type I (BD), and normal control (NC) subjects using mRNA gene expression signatures. A total of 90 subjects (n = 30 each for the three groups of subjects) provided blood samples at two visits. The Affymetrix exon microarray was used to profile the expression of over 1.4 million probesets. We selected potential biomarker panels using the temporal stability of the probesets and also back-tested them at two different visits for each subject. The 18-gene biomarker panels, using logistic regression modeling, correctly differentiated the three groups of subjects with high accuracy across the two different clinical visits (83–88% accuracy). The results are also consistent with the actual data and the “leave-one-out” analyses, indicating that the models should be predictive when applied to independent data cohorts. Many of the SZ and BD subjects were taking antipsychotic and mood stabilizer medications at the time of blood draw, raising the possibility that these drugs could have affected some of the differential transcription signatures. Using an independent Illumina data set of gene expression data from antipsychotic medication-free SZ subjects, the 18-gene biomarker panels produced a receiver operating characteristic curve accuracy greater than 0.866 in patients that were less than 30 years of age and medication free. We confirmed select transcripts by quantitative PCR and the nCounter® System. The episodic nature of psychiatric disorders might lead to highly variable results depending on when blood is collected in relation to the severity of the disease/symptoms. We have found stable trait gene panel markers for lifelong psychiatric disorders that may have diagnostic utility in younger undiagnosed subjects where there is a critical unmet need. The study requires replication in subjects for ultimate proof of the utility of the differential diagnosis.

Accuracy of the number of previous episodes reported by patients with bipolar disorder

BackgroundThe number of previous episodes in patients with BD is a variable widely used for both clinical and research purposes. The aim of this study was to compare the number of episodes retrospectively reported by euthymic BD subjects with that registered by their psychiatrists during a follow-up period. MethodsFifty euthymic patients with BD and more than 2years of follow-up were retrospectively asked in a standardized fashion about the number of hypomanic/manic and depressive episodes suffered during that period. Patient-reported outcomes were compared with the number of episodes registered by psychiatrists in a life chart during the same period. ResultsThe mean follow-up of patients was 66.70months. There was a mean difference of 2.74 episodes between reports of patients' and psychiatrists' reports during the complete follow-up period; Intraclass correlation coefficient was 0.40 (CI95%=0.15–0.61). This difference increased with the duration of the follow-up period (R=0.33, p=0.023) and with the number of episodes occurred during that (R=0.32, p=0.023). The difference between patient-reported and clinician-rated in the number of depressive during the follow-up period was more pronounced in BDII than in BDI (Z=−2.47, p=0.014), and it correlated with the number of previous depressive episodes at baseline (R=0.28, p=0.047) and subclinical depressive symptoms (R=0.41, p=0.003). ConclusionsThe number of previous episodes referred by patients with BD is not an accurate measure of the true number of episodes suffered. The theoretical and practical implications of these findings are discussed.

Uric acid levels may be a biological marker for the differentiation of unipolar and bipolar disorder: The role of affective temperament

BackgroundThe aim of this study was to investigate whether uric acid levels are different between patients with remission period of bipolar disorder type I (BD) and patients with remission period of major depressive disorder (MDD). MethodsFor this aim 41 patients diagnosed with BD and 30 patients diagnosed with recurrent MDD according to DSM-IV who were in remission period for at least 8 weeks were evaluated consecutively. The median age and gender distribution of the two groups were similar. Subjects with comorbid psychiatric diagnosis and/or severe medical illnesses were excluded. Affective temperament was evaluated with TEMPS-A (Temperament Evaluation of Memphis, Pisa, Paris and San Diego Autoquestionnaire). Plasma uric acid levels were recorded in mg/dl. ResultsThe uric acid levels of BD patients were found higher than patients with MDD and healthy controls. Additionally uric acid levels of MDD patients were lower than patients with BD and healthy subjects (F=4.183, p=0.039). A moderate correlation between hyperthymic and irritable temperament scores and uric acid levels was detected in both patient groups and in healthy controls. A negative correlation was observed between depressive temperament and uric acid levels only in MDD group. LimitationsThe measurements of temperament were estimated depending on the patient׳s statement. The medications that patients used were not controlled. ConclusionThere is a purinergic dysfunction not only in BD but also in MDD patients. High uric acid levels are associated with hyperthymic and irritable temperament scores whereas low uric acid levels are associated with depressive temperament scores.

Number of manic episodes is associated with elevated DNA oxidation in bipolar I disorder

Bipolar disorder (BD) is a major public health problem characterized by progressive functional impairment. A number of clinical variables have been associated with progression of the disease, most notably number of affective episodes and presence of psychotic symptoms, both of which correlate with greater cognitive impairment, lower response rates for lithium, and possibly lower levels of neurotrophic factors. Oxidative damage to cytosine and guanosine (8-OHdG) has been described as a modulator of DNA methylation, but the extent of DNA oxidative damage involvement in BD remains unclear. The aim of this study was to evaluate the extent of DNA oxidative damage to 8-OHdG and 5-methylcytosine (5-HMec), as well as global methylation (5-Mec), in BD patients and healthy controls. Potential association with clinical variables was also investigated. DNA levels of 8-OHdG, 5-HMec and 5-Mec were measured in 50 BD type I patients and 50 healthy controls. DNA 8-OHdG levels were higher in BD patients compared to healthy controls and found to be positively influenced by number of previous manic episodes. BD subjects had lower levels of 5-HMec compared to controls, whereas this measure was not influenced by the clinical features of BD. Number of manic episodes was correlated with higher levels of 8-OHdG, but not of 5-Mec or 5-HMec. Lower demethylation activity (5-HMec) but no difference in global 5-Mec levels was observed in BD. This finding suggests that oxidative damage to 8-OHdG might be a potential marker of disease progression, although further prospective cross-sectional studies to confirm neuroprogression in BD are warranted.

1842 – Severe mental illness and metabolic syndrome: a meta-analysis

Introduction People suffering from Severe Mental Illness (SMI) have a shorter life expectancy than general population. The excess of mortality may be primarily due to premature cardiovascular diseases. Subjects with a diagnosis of SMI may have an high prevalence of Metabolic Syndrome (MetS). Aim To estimate the risk of MetS among subjects with SMI compared to their counterpart without SMI. Methods A systematic review and meta-analysis of English and non-English articles using PubMed, Embase and PsycINFO was performed. ORs with related confidence intervals were used as association measures. All pooled analyses were based on random-effects models. Results The pooled analysis showed a statistically significant association for MetS in people suffering from SMI. However, we found a consistent level of heterogeneity between the included studies. Subanalyses showed that both SCZ and BD had higher risk than general population without SMI. No statistical differences were found comparing SCZ and BD subjects. Conclusions People with SMI have significantly higher risk to having MetS than general population. Despite some limitations, the results of present meta-analysis emphasize the relevance of a continuous cardio-metabolic assessment in the SMI population. Longitudinal researches are needed in order to assess the impact of a regular cardiovascular screening, prevention and treatment on the improvement of health status and life expectancy among people suffering from SMI.

Neuropsychology, social cognition and global functioning among bipolar, schizophrenic patients and healthy controls: preliminary data

This study aimed to determine the extent of impairment in social and non-social cognitive domains in an ecological context comparing bipolar (BD), schizophrenic (SKZ) patients and healthy controls (HC). The sample was enrolled at the Department of Psychiatry of Policlinico Hospital, University of Milan; it includes stabilized SKZ patients (n = 30), euthymic bipolar patients (n = 18) and HC (n = 18). Patients and controls completed psychiatric assessment rating scales, the Brief Assessment of Cognition in Schizophrenia (BACS) and the Executive and Social Cognition Battery (ESCB) that contains both ecological tests of executive function and social cognition, in order to better detect cognitive deficits in patients with normal results in standard executive batteries. The three groups differed significantly for gender and substance abuse, however, the differences did not influence the results. BD patients showed less impairment on cognitive performance compared to SKZ patients, even in “ecological” tests that mimic real life scenarios. In particular, BD performed better than SKZ in verbal memory (p < 0.0038) and BACS symbol coding (p < 0.0043). Regarding the ESCB tests, in the Hotel task SKZ patients completed significantly less tasks (p < 0.001), showed a greater number of errors in Multiple Errands Test (MET-HV) (p < 0.0248) and a worse performance in Theory of Mind (ToM) tests (p < 0.001 for the Eyes test and Faux pas test). Both patients' groups performed significantly worse than HC. Finally, significant differences were found between the two groups in GAF scores, being greater among BD subjects (p < 0.001). GAF was correlated with BACS and ESCB scores showing the crucial role of cognitive and ecological performances in patients' global functioning.

Impulsivity, aggression and suicidal behavior in unipolar and bipolar disorders

Predictors of suicidal behaviors (SB) in bipolar (BD) and major depressive disorder (MDD) patients are poorly understood. It has been recognized that behavioral dysregulation characterizes SB with traits of impulsivity and aggression being particularly salient. However, little is known about how these traits are segregated among mood disorder patients with and without a history of suicide attempt (SA). This article aims to compare impulsivity and aggression between 143 controls, 138 BD and 186 MDD subjects with or without a history of SA. BD and MDD patients showed higher impulsivity scores (BIS-10 = 57.9 vs. 44.7, p < 0.0001) and more severe lifetime aggression than controls (Lifetime History of Aggression = 7.3 vs. 3.9, p < 0.0001). Whereas impulsivity helped to distinguish MDD subjects without a history of SA from those with such a history, this was not the case in BD subjects where no difference in impulsive traits was observed between BD without and with history of SA (57.2 vs. 63.2 for BIS-10; p = 0.259). Impulsive and aggressive traits were strongly correlated in suicide attempters (independently of the diagnosis) but not in non-suicide attempters. Dimensional traits were not characterized at different stages of illness. Impulsivity, as a single trait, may be a reliable suicide risk marker in MDD but not in BD patients, and its strong correlation with aggressive traits seems specifically related to SB. Our study therefore suggests that the specific dimension of impulsive aggression should be systematically assessed in mood disorder patients to address properly their suicidal risk.

Increased rates of white matter hyperintensities in late‐onset bipolar disorder

Magnetic resonance imaging (MRI) studies have reported an increased frequency of white matter hyperintensities (WMH) in association with late-onset (LO) depression, and this has supported the notion that vascular-related mechanisms may be implicated in the pathophysiology of LO mood disorders. Recent clinical studies have also suggested a link between LO bipolar disorder (LO-BD) and cerebrovascular risk factors, but this has been little investigated with neuroimaging techniques. In order to ascertain whether there could be a specific association between WMH and LO-BD, we directly compared WMH rates between LO-BD subjects (illness onset >or= 60 years), early-onset BD subjects (EO-BD, illness onset <60 years), and elderly healthy volunteers. T2-weighted MRI data were acquired in LO-BD subjects (n = 10, age = 73.60 +/- 4.09), EO-BD patients (n = 49, age = 67.78 +/- 4.44), and healthy subjects (n = 24, age = 69.00 +/- 7.22). WMH rates were assessed using the Scheltens scale. There was a greater prevalence of WMH in LO-BD patients relative to the two other groups in the deep parietal region (p = 0.018) and basal ganglia (p < 0.045). When between-group comparisons of mean WMH scores were conducted taking account of age differences (ANCOVA), there were more severe scores in LO-BD patients relative to the two other groups in deep frontal and parietal regions, as well as in the putamen (p < 0.05). Our results provide empirical support to the proposed link between vascular risk factors and LO-BD. If extended in future studies with larger samples, these findings may help to clarify the pathophysiological distinctions between bipolar disorder emerging at early and late stages of life.

Processing of Differentially Valued Rewards and Punishments in Youths with Bipolar Disorder or Severe Mood Dysregulation

Youths with chronic irritability and hyperarousal (i.e., severe mood dysregulation, SMD) have reward- and punishment-processing deficits distinct from those exhibited by children with episodic symptoms of mania (i.e., narrow-phenotype bipolar disorder, BD). Additionally, youths with SMD, like those with psychopathy, have prominent reactive aggression. Therefore, we hypothesized that SMD, but not BD, youths would be impaired on a decision-making task that has identified reward- and punishment-processing deficits in individuals with psychopathy. A decision-making task was used in which BD (n = 23), SMD (n = 37), and control subjects (n = 31) were asked to choose between two images associated with different levels of reward or punishment. No between-group differences in task performance were found. These results suggest that BD, SMD, and normal youths do not differ in their ability to select between rewards and punishments of different value. Effect-size analyses suggest that this finding is not secondary to a type II error. Unlike individuals with psychopathy, neither SMD subjects nor those with BD differ from controls in their ability to select between differentially valued rewards and punishments.

Executive deficits in psychotic and bipolar disorders – Implications for our understanding of schizoaffective disorder

ObjectiveSchizoaffective disorder could be considered as a form of schizophrenia, a form of bipolar disorder, an independent disorder or a disorder intermediate between bipolar disorder and schizophrenia, within a psychotic continuum. The study of cognitive deficits in subjects with those diagnoses could help differentiate between these possibilities. MethodsWe compared cognitive performances of schizoaffective (SZAff) subjects with those of subjects with schizophrenia (SZ), bipolar disorder with psychotic symptoms (life-time) (BDP), bipolar disorder without life-time occurrence of psychotic symptoms (BD) and normal controls (NC). We used two tests of executive functions – the Wisconsin Card Sorting Test (WCST) and the Trail-making Test (TMT) – that are known to be impaired in those disorders. ResultsThe number of perseverative errors on WCST was highest in SZ subjects and gradually decreased in SZAff, BDP and, finally in BD subjects. By contrast, SZ and SZAff subjects obtained similar scores in the TMT, as did BD and BDP patients. ConclusionsThese results suggest that, for some deficits, there may be a continuum between SZ, SZAff and affective disorders, whereas SZAff patients most closely resemble SZ patients for other deficits. This implies that different conceptual views about schizoaffective disorder should be seen as complementary, rather than mutually exclusive.

Mismatch between self-reported quality of life and functional assessment in acute mania: A matter of unawareness of illness?

Background Studies addressing self-reported quality of life (QoL) in acute mania are scarce and inconsistent. While it has been suggested that there is some disagreement between objective measures and subjective QoL as reported by acutely manic patients, this issue has not been systematically studied. This study aims to investigate the self-reported QoL in manic, depressed, and euthymic BD subjects, as compared to matched healthy controls. Methods One-hundred and twenty type-I bipolar patients (40 manic, 40 depressed, and 40 euthymic) and 40 matched controls were studied. Self-reported QoL was assessed using the World Health Organization's Quality of Life Instrument-Short Version (WHOQOL-BREF). Objective functioning was assessed using the Global Assessment of Functioning (GAF), and depressive and manic symptoms were assessed using the Hamilton Depression Rating Scale-17 items (HDRS) and the Young Mania Rating Scale (YMRS), respectively. Results Manic patients presented the lowest GAF measures but reported same overall QoL as euthymic patients and controls, and better QoL than depressed patients. Within the manic subgroup, there was a significant inverse correlation between psychological QoL and GAF scores ( r = − 0.54; p = 0.001). Limitations The cross-sectional design and the lack of control for potential comorbid conditions are the major limitations of the present study. Conclusions Our findings suggest that this mismatch between objective and subjective measures during acute mania may be associated with a lack of insight or awareness of their own illness.

Glucose metabolism in the amygdala in depression: Relationship to diagnostic subtype and plasma cortisol levels

In a previous positron emission tomography (PET) study of major depression, we demonstrated that cerebral blood flow was increased in the left amygdala in unipolar depressives with familial pure depressive disease (FPDD) relative to healthy controls [J. Neurosci. 12 (1992) 3628.]. These measures were obtained from relatively low-resolution PET images using a stereotaxic method based upon skull X-ray landmarks. The current experiments aimed to replicate and extend these results using higher-resolution glucose metabolism images and magnetic resonance imaging (MRI)-based region-of-interest (ROI) analysis. The specificity of this finding to FPDD was also investigated by assessing depressed samples with bipolar disorder (BD-D) and depression spectrum disease (DSD). Finally, the relationship between amygdala metabolism and plasma cortisol levels obtained during the scanning procedure was assessed. Glucose metabolism was measured using PET and 18F-fluorodeoxyglucose ( 18FDG) in healthy control ( n=12), FPDD ( n=12), DSD ( n=9) and BD-D ( n=7) samples in the amygdala and the adjacent hippocampus. The left amygdala metabolism differed across groups ( P<.001), being increased in both the FPDD and BD-D groups relative to the control group. The left amygdala metabolism was positively correlated with stressed plasma cortisol levels in both the unipolar ( r=.69; P<.005) and the bipolar depressives ( r=0.68; .1< P<.05). In contrast, neither significant main effects of diagnosis nor significant relationships with plasma cortisol were evident in post hoc analyses of metabolism in the right amygdala or the hippocampus. Preliminary assessment of BD subjects imaged during remission suggested that amygdala metabolism is also elevated in remitted subjects who are not taking mood-stabilizing drugs, but within the normal range in subjects taking mood stabilizers. These data confirm our previous finding that neurophysiological activity is abnormally increased in FPDD, and extend it to BD-D. These abnormalities were not accounted for by spilling in of radioactivity from the adjacent hippocampus. The correlation between left amygdala metabolism and stressed plasma cortisol levels may conceivably reflect either the effect of amygdala activity on corticotropin-releasing hormone (CRH) secretion or the effect of cortisol on amygdala function.

289. - Elevated intracellular calcium in transformed lymphoblasts in bipolar I disorder

dPK). a tetrameric protein composed of 2 regulatory and catalytic subunits, is the primary targetor intracellular cAMPsignalling, and the levels of some cAMP·dPK regulatory subunit isoforms may be moduluted by changes in cytosolic cAMP levels consequent 10 activation or receptors coupled to this second messenger, In the present study. we assessed whether[iH)cAMP binding. a measure of cAMP-dPK regulatory subunit levels. is altered in cortical regions of postmortem BDbrains in which higher GOl~ protein levels have been previously identified. eH)cAMPbinding measured in cytosolic and membrane fractions from postmortem temporal cortex by the procedure of (Takeda et nl,J Biochen: 105:327-329, 1989), was saturable and specific with Kd values of 0.89 ± 0.1 nM(sltc I) and 3.6 :!: 0.47 nM (:tile 2). and Brnax of 154 :!: 28,26 fmoVms r,rotein (site I) and 283 :t 36.49 fmoUmg prolein (sile 2). Specific [ HlcAMP (S nM)binding wasestimated both on cytosolic and membrane fractions from frontal, temporal, parietal, and occipital cortices.and cerebellum and thalamus of postmortem brain from 10 patients with BD compared with age and postmortem-delay matched controls, (JHleAMP binding was significantly reduced (-28%, p =: O.()4) in cytosollc fractions from BO temporal cortex compared lith matched controls. A trendtoward decreased [;1H]cAMP binding was also observed in cytosolic fractions from frontal (-23%). parietal (-18%) and occipital (-26%) cortex, and cerebellum (-35%), but not in thalamus. In contrast, ['H!cAMP. binding was not slgniflcamly different between BD and control subjects in membrane fraeuons of theregions examined. Lithium levels measured in temporal cortex correlated slgnlficantly with 13HlcAMP binding in temporal cortex (r= 0.68,p=O.03) and cerebellum (r=0.86, p=0.02) of BO brain. These results suggest that decreased cytosolic cAMP-dPK levels found in postmortem BD brain may be a result of antemortem lithium andlor mood stabilizer treatment and may notreflect enhanced cAMP signnlJing per se, Supported by the MRC and Clarke Institute Research Foundation.