Remitted Subjects Research Articles

Mania associated olfactory dysfunction: A comparison between bipolar subjects in mania and remission

ObjectivesThe aim of this study was to assess the olfactory functions of patients with bipolar disorder in manic phase and to compare them to those of bipolar subjects in remission and healthy controls. MethodsWe recruited 96 participants divided in 3 groups: bipolar mania (MB), euthymic bipolar in remission (EB) and healthy controls (HC). All participants underwent an assessment of their olfactory functions using the Sniffin’ sticks threshold and identification tests. Odors' pleasantness, intensity, familiarity and emotion were assessed. All participants were screened for the presence of psychiatric disorder through the MINI questionnaire. Clinical evaluation explored dimensions of mania, depression, anxiety respectively through YMRS, MADRS and STAI scales. Anhedonia was explored through the Chapman physical and social anhedonia questionnaire. ResultsPatients in mania had deficits in identifying positive smells compared to bipolar subjects in remission and to healthy controls (MB < EB < HC; p < 0.001). Hedonic (MB < EB = HC; p < 0.001) and emotional (MB < EB = HC; p < 0.001) ratings of positive smells were lower in patients in manic phase compared to remitted subjects or controls. Mania was associated to higher emotion rating of negative smells compared to remitted subjects and controls (MB > EB = HC; p < 0.001). There was no difference between the 3 groups in the ratings of intensity and familiarity of smells, as well as in the olfactory threshold testing. The 3 groups showed no difference in the identification of negative smells. ConclusionsPatients in manic episodes showed deficits in identifying positive odors. They evaluated these smells as less pleasant and less emotional compared to remitted bipolar subjects and healthy controls. These olfactory dysfunctions may constitute potential indicators of manic state. The persistence of olfactory dysfunction in remission phase (deficit in the olfactory identification of positive odors compared to healthy controls) may constitute a potential trait indicator of bipolarity.

Aripiprazole as First-Line Therapy for Late-Life Depression: A Case Note Review.

Aripiprazole, structurally considered a third-generation antipsychotic agent, is an effective adjuvant strategy for managing treatment-resistant depression. It has been used successfully as an add-on agent in late-life depression (LLD), but there are no controlled trials on its use as first-line therapy, either alone or in combination with an antidepressant. This is a case note review of aripiprazole prescribed to outpatients with LLD as a first-line therapy either in combination with an antidepressant or as a monotherapy. The local ethics committee approved the audit. Case notes of subjects with Hamilton Rating Scale for Depression scores of ≥11 and with at least 1 follow-up visit were included in the review. Remission was defined as the first occurrence of achieving a Hamilton Rating Scale for Depression score of <10. Case notes of 54 subjects (mean age, 68.6 ± 6.9 years) were included, 52 of whom had unipolar depression. Aripiprazole alone was prescribed in 21 subjects, and with an antidepressant in the remaining subjects. The overall remission rate was 59% over 21 weeks, and in the remitted subjects (n = 32), the cumulative remission rate increased from 22% at week 2 to 82% at week 10. No subject discontinued treatment because of poor tolerability or serious adverse events. Aripiprazole was found to be an effective first-line antidepressant in LLD. The remission rates in the present study were considerably higher than the published literature on antidepressant monotherapy in fresh episodes of LLD. This warrants controlled trials of aripiprazole as a first-line antidepressant for this disease entity.

Avoidant Attachment Style Moderates the Recovery of Healthy Sexuality in Women With Anorexia Nervosa Treated With Enhanced Cognitive Behavior Therapy (CBT-E): A 2-Year Follow-Up Study

Insecure Attachment style has been associated with interpersonal problems in persons with Anorexia Nervosa (AN), and it might moderate the recovery of healthy sexuality in these subjects. The aim of the present 2-year follow-up study was to evaluate the role of insecure attachment style as a moderator of the recovery of healthy sexuality in women with AN. 63 Italian women with AN treated with a multidisciplinary approach including Enhanced Cognitive Behavior Therapy were evaluated by means of a clinical interview and self-administered questionnaires. Individual psychotherapy sessions were administered by experienced psychotherapists over the course of at least 40 weeks (median number of sessions=43, range: 38-50); trained dieticians provided personalized nutritional counselling to facilitate weight recovery. The assessment was performed at baseline (T0) and after 1 (T1) and 2 (T2) years. The administered questionnaires investigated general psychopathology (SCL-90-R), eating disorder-specific psychopathology (EDE-Q), female sexuality (FSFI) and adult attachment style (ECR). At baseline, avoidant attachment style was associated with all domains of sexual dysfunction. Longitudinal analysis showed a significant decrease in both eating disorder-specific psychopathology and sexual dysfunctions at follow-up evaluations. However, only 45% of remitted subjects also recovered healthy sexuality: these women reported significantly lower avoidance scores than those who only recovered from AN. Moderation analysis indicated that sexual desire did not increase in participants with higher levels of avoidant attachment. These novel findings highlighted the importance of the assessment of adult attachment in the clinical setting, for better characterization and treatment of persons suffering from AN. The long follow-up duration, the multidisciplinary nature of the treatment, and the novelty of the topic were major strengths of the study, whereas the limited sample size and the absence of biological data were the main limitations. This study highlighted the crucial role of avoidant attachment in the relationship between AN and sexual dysfunctions, underlining the importance of integrating treatments with attachment-focused interventions. Cassioli E, Rossi E, Vizzotto C, et al. Avoidant Attachment Style Moderates the Recovery of Healthy Sexuality in Women With Anorexia Nervosa Treated With Enhanced Cognitive Behavior Therapy (CBT-E): A 2-Year Follow-Up Study. J Sex Med 2022;19:347-355.

Distinguishing medication-free subjects with unipolar disorder from subjects with bipolar disorder: state matters.

Recent studies have indicated that pattern recognition techniques of functional magnetic resonance imaging (fMRI) data for individual classification may be valuable for distinguishing between major depressive disorder (MDD) and bipolar disorder (BD). Importantly, medication may have affected previous classification results as subjects with MDD and BD use different classes of medication. Furthermore, almost all studies have investigated only depressed subjects. Therefore, we focused on medication-free subjects. We additionally investigated whether classification would be mood state independent by including depressed and remitted subjects alike. We applied Gaussian process classifiers to investigate the discriminatory power of structural MRI (gray matter volumes of emotion regulation areas) and resting-state fMRI (resting-state networks implicated in mood disorders: default mode network [DMN], salience network [SN], and lateralized frontoparietal networks [FPNs]) in depressed (n=42) and remitted (n=49) medication-free subjects with MDD and BD. Depressed subjects with MDD and BD could be classified based on the gray matter volumes of emotion regulation areas as well as DMN functional connectivity with 69.1% prediction accuracy. Prediction accuracy using the FPNs and SN did not exceed chance level. It was not possible to discriminate between remitted subjects with MDD and BD. For the first time, we showed that medication-free subjects with MDD and BD can be differentiated based on structural MRI as well as resting-state functional connectivity. Importantly, the results indicated that research concerning diagnostic neuroimaging tools distinguishing between MDD and BD should consider mood state as only depressed subjects with MDD and BD could be correctly classified. Future studies, in larger samples are needed to investigate whether the results can be generalized to medication-naïve or first-episode subjects.

Visuospatial planning in unmedicated major depressive disorder and bipolar disorder: distinct and common neural correlates.

Cognitive impairments are an important feature of both remitted and depressed major depressive disorder (MDD) and bipolar disorder (BD). In particular, deficits in executive functioning may hamper everyday functioning. Identifying the neural substrates of impaired executive functioning would improve our understanding of the pathophysiology underlying these disorders, and may eventually aid in discriminating between MDD and BD, which is often difficult during depression and remission. To date, mostly medicated MDD and BD subjects have been investigated, which may have influenced results. Therefore, we investigated executive functioning in medication-free depressed and remitted MDD and BD subjects. We used the Tower of London (ToL) visuospatial planning task to assess behavioural performance and blood oxygen-level dependent responses in 35 healthy controls, 21 remitted MDD, 23 remitted BD, 19 depressed MDD and nine depressed BD subjects. Visuospatial planning per se was associated with increased frontostriatal activity in depressed BD compared to depressed MDD. In addition, post-hoc analyses indicated that visuospatial planning load was associated with increased parietal activity in depressed compared to remitted subjects, and BD compared to MDD subjects. Task performance did not significantly differ between groups. More severely affected, medication-free mood disorder patients require greater parietal activity to perform in visuospatial planning, which may be compensatory to maintain relatively normal performance. State-dependent frontostriatal hyperactivity during planning may be a specific BD characteristic, providing clues for further characterization of differential pathophysiology in MDD v. BD. This could potentially provide a biomarker to aid in the differentiation of these disorders.

Proton magnetic resonance spectroscopy revealed differences in the glutamate + glutamine/creatine ratio of the anterior cingulate cortex between healthy and pediatric post-traumatic stress disorder patients diagnosed after 2008 Wenchuan earthquake.

Earthquakes always leave many surviving teenagers suffering from various mental problems, such as post-traumatic stress disorder (PTSD). We studied the metabolites in current and remitted pediatric PTSD patients and healthy controls after an earthquake, aiming to find the neurochemistry differences in these teenagers. Proton magnetic resonance spectroscopy ((1) H-MRS) was performed in the anterior cingulate cortex (ACC) of 21 healthy, 10 PTSD and 23 remitted subjects. Significantly lower glutamate + glutamine/creatine (Glx/Cr) levels in the ACC (1.15 ± 0.14 vs 1.37 ± 0.08, P = 0.047) were found in PTSD subjects relative to remitted subjects; and significantly lower Glx/Cr levels in the ACC (1.37 ± 0.08 vs 1.59 ± 0.10, P = 0.045) were found in remitted subjects relative to healthy controls. Our findings imply that the Glx/Cr ratio in the ACC can be used to differentiate not only between healthy and pediatric PTSD patients, but also between the current and remitted phases of pediatric PTSD. The changes in the Glx/Cr ratio may be caused by brain dysfunction in the current phase and recovery in the remitted phase.

Co-morbid Psychiatric Symptoms Influencing the Metabolic Syndrome in Patients Treated with Long Acting Injectable Antipsychotics

Introduction In patients receiving long acting injectable (LAI) antipsychotics, the risk of medication side effects needs serious attention. Objectives The study objective is to determine in which measure co-morbid psychiatric symptoms influence the presence of the metabolic syndrome (MS). Aims Patients receiving LAI antipsychotics have a history of medication non-adherence, with recurrences and partial remissions. The aim of the study is to assess the contribution of residual psychiatric symptoms in the development of the MS in these patients. Methods The study includes two samples of psychotic remitted subjects, one including patients on olanzapine LAI and the other one patients receiving risperidone LAI for at least six months. The presence of co-morbid symptoms was assessed with BPRS. The International Federation of Diabetes diagnostic criteria for the MS were used. The following information was analyzed: medication, gender, fasting glycemia, lipid profile, waist circumference, blood pressure, and psychiatric symptoms. Results The study included 28 patients, 15 (53.6%) on olanzapine LAI, and 13 (46.4%) on risperidone LAI. 15 patients were women and 13 men. 11 (39.2%) patients were diagnosed with MS. The whole sample presented higher scores at the following BPRS items: anxiety, somatic concern, and motor retardation. Conclusions Symptoms such as anxiety, somatic concern, and motor retardation may contribute to the development of the MS. 39% of the subjects presented the criteria of the MS.

Adverse effects including sexual problems associated with the use of selective serotonin reuptake inhibitors in a tertiary care center of Eastern Nepal

Background: Selective serotonin reuptake inhibitors (SSRIs) use has been associated with various adverse drug events, including sexual problems in recent literature. Methods: After written informed consent, remitted psychiatric patients were enrolled if they were taking an SSRI. The remitted state was ascertained by clinical assessment of a psychiatrist and reassessed with the use of self-response screening questionnaires (Beck Anxiety Inventory for anxiety, Beck Depression Inventory for depression). The self-response questionnaire “adverse drug effect (ADE) tool” was used to assess ADEs and the Arizona Sexual Experience Scale to assess sexual problems. Results: The total of 200 subjects was enrolled with 63% females. Commonly used SSRIs were escitalopram, fluoxetine, and sertraline for the common diagnosis of depression, recurrent depressive disorder, and panic disorder in this institute. The average duration of remission during the enrollment was 11.99 months (standard deviation: 12.269). The overall prevalence of adverse effects was 91.5%. The incidence of adverse effect and sexual problem were: weight gain (57%), dryness of mouth (32.5%), headache (30%), dizziness (28.5%), paresthesia (24.5%), confusion (23.5%), tremors (21.5%), irritation (20.5%) sexual dysfunction (SD) (17.2%), increase in anxiety (17%), akathisia (16%), nausea (14.5%), itchiness (14.5%), excessive sweating, (14.5%), difficulty in sleeping (10%), weight loss (6%), rash (6%), diarrhea (4%), vomiting (3%), and others (3%). Conclusion: Adverse effect (irrespective of severity) was commonly seen with SSRI use. Common adverse effects seen among remitted subjects were weight gain, dryness of mouth, headache, dizziness, paresthesia, etc. SD was other important side effect.

Increased cortisol awakening response was associated with time to recurrence of major depressive disorder.

Although HPA-axis activity has been studied extensively in relation to depression, there is no consensus whether HPA-axis parameters predicts major depressive disorder (MDD) recurrence. We investigated whether HPA-axis parameters (cortisol awakening response (CAR), the dexamethasone suppression test (DST) and evening cortisol) predict time to recurrence in remitted subjects with a history of MDD and whether childhood trauma and life events interact with HPA-axis parameters in increasing the risk for recurrence. Data were derived from 549 subjects with a lifetime diagnosis of MDD in remission for at least six months preceding the baseline assessment of the Netherlands Study of Depression and Anxiety (NESDA). Subjects were followed up with two interviews over the course of four years to assess recurrence. DSM-IV based diagnostic interviews were used to assess time to recurrence of MDD. Seven salivary cortisol samples collected at baseline with information on CAR, evening cortisol and the DST. Hazard ratios were calculated using Cox regression analysis, adjusted for covariates. A higher CAR was associated with time to recurrence of MDD (HR=1.03, 95%CI 1.003-1.060, p=0.03) whereas evening cortisol and DST were not. No interactions between HPA-axis parameters and stress-related factors were found. Our data support previous studies reporting that subjects with a higher CAR are more vulnerable to recurrence of MDD.

Lower serum brain-derived neurotrophic factor levels are associated with failure to achieve remission in patients with major depression after escitalopram treatment.

BackgroundRemission, the primary goal of treatment for major depressive disorder (MDD), is the absence of significant signs or symptoms and the return to a state of normal functioning. A recent study found that the level of brain-derived neurotrophic factor (BDNF) increased after antidepressant treatment in remitted patients. This study evaluated serum BDNF levels in MDD patients with chronic maintenance treatment, and compared these between remission and nonremission groups.Materials and methodsSerum BDNF levels were measured in 34 MDD patients and 35 healthy controls. The severity of depression was measured using the Hamilton Depression Rating Scale (Ham-D). The MDD patients were divided into remission and nonremission groups according to a cutoff total Ham-D score of either ≤7 or ≤6.ResultsSerum BDNF levels differed significantly between the remission, nonremission, and healthy control groups (P<0.05). The Bonferroni post hoc test confirmed that serum BDNF levels were significantly lower in the nonremission group than in the healthy-control group (P<0.05), but did not differ significantly between the remission and healthy-control groups.LimitationsThis study included a small sample, and measured serum BDNF levels in the MDD patients at only one point during the maintenance treatment.ConclusionThis study found that serum BDNF levels during maintenance treatment were lower in MDD patients with failure to achieve remission than in controls, while the remitted subjects had normalized serum BDNF levels. A lower level of serum BDNF during maintenance treatment is associated with failure to achieve remission in patients with major depression. Moreover, serum BDNF levels after chronic antidepressant treatment can be used as a biological marker for detecting nonremission.

The effects of catecholamine depletion on the neural response to fearful faces in remitted depression.

Recent evidence suggests that increased psychophysiological response to negatively valenced emotional stimuli found in major depressive disorder (MDD) may be associated with reduced catecholaminergic neurotransmission. Fourteen unmedicated, remitted subjects with MDD (RMDD) and 13 healthy control subjects underwent catecholamine depletion with oral α-methyl-para-tyrosine (AMPT) in a randomized, placebo-controlled, double-blind crossover trial. Subjects were exposed to fearful (FF) and neutral faces (NF) during a scan with [15O]H2O positron emission tomography to assess the brain-catecholamine interaction in brain regions previously associated with emotional face processing. Treatment with AMPT resulted in significantly increased, normalized cerebral blood flow (CBF) in the left inferior temporal gyrus (ITG) and significantly decreased CBF in the right cerebellum across conditions and groups. In RMDD, flow in the left posterior cingulate cortex (PCC) increased significantly in the FF compared to the NF condition after AMPT, but remained unchanged after placebo, whereas healthy controls showed a significant increase under placebo and a significant decrease under AMPT in this brain region. In the left dorsolateral prefrontal cortex (DLPFC), flow decreased significantly in the FF compared to the NF condition under AMPT, and increased significantly under placebo in RMDD, whereas healthy controls showed no significant differences. Differences between AMPT and placebo of within-session changes in worry-symptoms were positively correlated with the corresponding changes in CBF in the right subgenual prefrontal cortex in RMDD. In conclusion, this study provided evidence for a catecholamine-related modulation of the neural responses to FF expressions in the left PCC and the left DLPFC in subjects with RMDD that might constitute a persistent, trait-like abnormality in MDD.

Chronic Treatment with the 5-HT1A Receptor Partial Agonist Tandospirone Increases Hippocampal Neurogenesis.

IntroductionA large-scale clinical trial, the Sequence Trial Alternatives to Relieve Depression (STAR*D) study, concluded that about one-third of the studied patients with major depressive disorder remitted during the initial treatment with selective serotonin reuptake inhibitors and that approximately half of the remitted subjects relapsed over a 1-year follow-up. The development of new therapeutic approaches with potent efficacy and good tolerability for the treatment of depressive disorders is of great importance. Adult hippocampal neurogenesis has been proposed to be important for understanding and treating depression and anxiety. The present study aimed to elucidate whether or not 5-hydroxytryptamine 1A (5-HT1A) receptor partial agonists have a potential therapeutic effect for the treatment of depressive and anxiety disorders, from the standpoint of neurogenesis.MethodsMale Sprague–Dawley rats were subcutaneously administered a vehicle or tandospirone (TDS) (1 or 10 mg/kg) once daily for 14 days. The effects of chronic TDS treatment on neurogenesis were evaluated on the day after the last injection. The quantification of hippocampal neurogenesis was estimated using immunostaining with doublecortin (DCX), a marker protein of newborn neurons.ResultsChronic TDS treatment resulted in a significant increase in the number of DCX-positive cells per volume of dentate gyrus in a dose-dependent manner.ConclusionThe results strongly suggest that 5-HT1A receptor partial agonists would be useful and beneficial in the treatment of depressive and anxiety disorders through increased hippocampal neurogenesis.Electronic supplementary materialThe online version of this article (doi:10.1007/s40120-013-0015-0) contains supplementary material, which is available to authorized users.

Is it true remission? A study of remitted patients affected by schizophrenia and schizoaffective disorders

To date, few studies have reported analytical data relating to clinical remission, functional remission and subjective experience. The present study aimed to investigate these aspects in a sample of chronic outpatients. Methods: 112 schizophrenic or schizoaffective outpatients (Males=60; Females=52; mean age 43.5±9.42yr) were evaluated with regard to symptomatology (SCID-I; PANSS, CGI-SCH scales), functioning (PSP scale), subjective wellbeing (SWN-K scale) and Quality of Life (WHO-QoL-Bref scale). Results: 50% of patients were found to be in remission. Significantly higher scores at PANNS, CGI-SCH, PSP, but not at SWN and WHO-QoL, were found among remitted patients; a relevant proportion of remitted subjects continued to manifest a moderate level of symptoms (score >3) both at PANSS (35% of cases) and CGI-SCH (29% of cases), significant functional impairment (total score <70) at PSP (68% of cases ), and a lesser degree of wellbeing (total score <80) at SWN-K (34% of cases). Conclusion: patients in whom clinical remission was confirmed may display persisting symptoms, relevant areas of functional impairment and a decreased sense of wellbeing.

Dopamine-Related Deficit in Reward Learning After Catecholamine Depletion in Unmedicated, Remitted Subjects with Bulimia Nervosa

Disturbances in reward processing have been implicated in bulimia nervosa (BN). Abnormalities in processing reward-related stimuli might be linked to dysfunctions of the catecholaminergic neurotransmitter system, but findings have been inconclusive. A powerful way to investigate the relationship between catecholaminergic function and behavior is to examine behavioral changes in response to experimental catecholamine depletion (CD). The purpose of this study was to uncover putative catecholaminergic dysfunction in remitted subjects with BN who performed a reinforcement-learning task after CD. CD was achieved by oral alpha-methyl-para-tyrosine (AMPT) in 19 unmedicated female subjects with remitted BN (rBN) and 28 demographically matched healthy female controls (HC). Sham depletion administered identical capsules containing diphenhydramine. The study design consisted of a randomized, double-blind, placebo-controlled crossover, single-site experimental trial. The main outcome measures were reward learning in a probabilistic reward task analyzed using signal-detection theory. Secondary outcome measures included self-report assessments, including the Eating Disorder Examination-Questionnaire. Relative to healthy controls, rBN subjects were characterized by blunted reward learning in the AMPT--but not in placebo--condition. Highlighting the specificity of these findings, groups did not differ in their ability to perceptually distinguish between stimuli. Increased CD-induced anhedonic (but not eating disorder) symptoms were associated with a reduced response bias toward a more frequently rewarded stimulus. In conclusion, under CD, rBN subjects showed reduced reward learning compared with healthy control subjects. These deficits uncover disturbance of the central reward processing systems in rBN related to altered brain catecholamine levels, which might reflect a trait-like deficit increasing vulnerability to BN.

Brain correlates of craving for online gaming under cue exposure in subjects with Internet gaming addiction and in remitted subjects

This study aimed to evaluate brain correlates of cue-induced craving to play online games in subjects with Internet gaming addiction (IGA), subjects in remission from IGA and controls. The craving response was assessed by event-related design of functional magnetic resonance images (fMRIs). Fifteen subjects with IGA, 15 in remission from IGA and 15 controls were recruited in this study. The subjects were arranged to view the gaming screenshots and neutral images under investigation of fMRIs. The results showed that bilateral dorsolateral prefrontal cortex (DLPFC), precuneus, left parahippocampus, posterior cingulate and right anterior cingulate were activated in response to gaming cues in the IGA group and their activation was stronger in the IGA group than those in the control group. Their region-of-interest was also positively correlated with subjective gaming urge under cue exposure. These activated brain areas represent the brain circuit corresponding to the mechanism of substance use disorder. Thus, it would suggest that the mechanism of IGA is similar to substance use disorder. Furthermore, the IGA group had stronger activation over right DLPFC and left parahippocampus than did the remission group. The two areas would be candidate markers for current addiction to online gaming and should be investigated in future studies.

Elevated Left and Reduced Right Orbitomedial Prefrontal Fractional Anisotropy in Adults With Bipolar Disorder Revealed by Tract-Based Spatial Statistics

Diffusion tensor imaging (DTI) studies in adults with bipolar disorder (BD) indicate altered white matter (WM) in the orbitomedial prefrontal cortex (OMPFC), potentially underlying abnormal prefrontal corticolimbic connectivity and mood dysregulation in BD. To use tract-based spatial statistics (TBSS) to examine WM skeleton (ie, the most compact whole-brain WM) in subjects with BD vs healthy control subjects. Cross-sectional, case-control, whole-brain DTI using TBSS. University research institute. Fifty-six individuals, 31 having a DSM-IV diagnosis of BD type I (mean age, 35.9 years [age range, 24-52 years]) and 25 controls (mean age, 29.5 years [age range, 19-52 years]). Fractional anisotropy (FA) longitudinal and radial diffusivities in subjects with BD vs controls (covarying for age) and their relationships with clinical and demographic variables. Subjects with BD vs controls had significantly greater FA (t > 3.0, P <or= .05 corrected) in the left uncinate fasciculus (reduced radial diffusivity distally and increased longitudinal diffusivity centrally), left optic radiation (increased longitudinal diffusivity), and right anterothalamic radiation (no significant diffusivity change). Subjects with BD vs controls had significantly reduced FA (t > 3.0, P <or= .05 corrected) in the right uncinate fasciculus (greater radial diffusivity). Among subjects with BD, significant negative correlations (P < .01) were found between age and FA in bilateral uncinate fasciculi and in the right anterothalamic radiation, as well as between medication load and FA in the left optic radiation. Decreased FA (P < .01) was observed in the left optic radiation and in the right anterothalamic radiation among subjects with BD taking vs those not taking mood stabilizers, as well as in the left optic radiation among depressed vs remitted subjects with BD. Subjects having BD with vs without lifetime alcohol or other drug abuse had significantly decreased FA in the left uncinate fasciculus. To our knowledge, this is the first study to use TBSS to examine WM in subjects with BD. Subjects with BD vs controls showed greater WM FA in the left OMPFC that diminished with age and with alcohol or other drug abuse, as well as reduced WM FA in the right OMPFC. Mood stabilizers and depressed episode reduced WM FA in left-sided sensory visual processing regions among subjects with BD. Abnormal right vs left asymmetry in FA in OMPFC WM among subjects with BD, likely reflecting increased proportions of left-sided longitudinally aligned and right-sided obliquely aligned myelinated fibers, may represent a biologic mechanism for mood dysregulation in BD.

Depressive State- and Disease-Related Alterations in Neural Responses to Affective and Executive Challenges in Geriatric Depression

Geriatric depression has been associated with a heterogeneous neuropathology. Identifying both depressive state-related and disease-related alterations in brain regions associated with emotion and cognitive function could provide useful diagnostic information in geriatric depression. Twelve late-onset acutely depressed patients, 15 patients fully remitted from major depression, and 20 healthy comparison subjects underwent event-related functional MRI. Brain activation and deactivation associated with executive and emotional processing were investigated using an emotional oddball task in which circles were presented infrequently as attentional targets and sad and neutral pictures as novel distractors. Significant changes in brain activation in patients were found mainly in response to attentional targets rather than to sad distractors. Relative to healthy comparison subjects, the depressed patients had attenuated activation in the regions of the executive system, including the right middle frontal gyrus, the cingulate, and inferior parietal areas. Activity in the middle frontal gyrus revealed depressive state-dependent modulation, whereas attenuated activation in the anterior portion of the posterior cingulate and inferior parietal regions persisted in the remitted subjects, suggesting a disease-related alteration. Enhanced deactivation was observed in the posterior portion of the posterior cingulate, which was also state dependent. The remitted group did not show this deactivation. Our results indicate distinct roles for the right middle frontal gyrus and the anterior and posterior portions of the posterior cingulate cortex in geriatric depression. The deactivation of the posterior portion of the posterior cingulate could be informative for differentiation of cognitive dysfunction related to depression from other conditions, such as mild cognitive impairment.

CURRENTLY ACTIVE AND REMITTED ALCOHOL DEPENDENCE IN A NATIONWIDE ADULT GENERAL POPULATION—RESULTS FROM THE FINNISH HEALTH 2000 STUDY

To study the factors relating to remission from alcohol dependence in the general population. Within a representative, cross-sectional general population sample aged 30 years or more, the characteristics of subjects remitted from alcohol dependence were examined by comparisons with actively alcohol-dependent subjects. The overall lifetime prevalence of alcohol dependence was 7.9%. Comorbid depressive and anxiety disorders were diagnosed in 22% of the actively alcohol-dependent and in 19% of the remitted subjects. There were few sociodemographic, clinical or childhood-related factors differentiating the two groups of subjects. Of comorbid mental disorders, social phobia (6% vs 1%) and dysthymia (7% vs 3%) were more common among the actively alcohol-dependent, whereas other common disorders were equally common for both active and remitted alcohol dependence. Health care or other service use for alcohol problems within the previous 12 months was more frequent among the actively dependent (16% vs 4%), and the same was true for health care use for mental health problems (17% vs 8%). Any service use in the previous year for either type of problem was more common among the actively dependent than the remitted (26% vs 13%). In an unselected setting, only comorbid social phobia and dysthymia differentiated active alcohol dependence from a remitted state, suggesting either that they are obstacles to remission from an active state, explaining why some alcohol-dependent individuals are unable to recover, or that their symptoms are maintained by excessive alcohol use. The actively alcohol-dependent used both substance use services and mental health services more often than the remitted subjects, possibly due to needs generated by their alcohol problem. Comorbid psychopathology should be considered when developing treatment options for alcohol dependence.

Impaired Recruitment of the Dorsolateral Prefrontal Cortex and Hippocampus During Encoding in Bipolar Disorder

The aim of the present study was to examine the functional neuroanatomy of episodic memory impairment in euthymic subjects with bipolar I disorder. There is evidence that individuals with bipolar disorder have cognitive impairments not only during mood episodes but also when they are euthymic. The most consistently reported cognitive difficulty in euthymic subjects with bipolar disorder is impairment in verbal episodic memory (i.e., the ability to learn new verbal information). The current study examined verbal learning in eight euthymic, remitted subjects with bipolar I disorder (BP-I; seven nonmedicated) and eight control subjects matched for age, gender, education, and intelligence. Subjects underwent (15)O-CO(2) positron emission tomography scanning while completing a verbal learning paradigm that consisted of encoding (learning) several lists of words. The BP-I subjects had more difficulties learning the lists of words compared with the control subjects. Compared with control subjects, BP-I subjects exhibited blunted regional cerebral blood flow (rCBF) increases in the left dorsolateral prefrontal cortex (Brodmann's area 9/46) during encoding. Consistent with previous studies, subjects with BP-I were impaired in learning new verbal information. This was associated with rCBF abnormalities in brain regions involved in learning and episodic memory.

Functional impairment in the remission phase of bipolar disorder

The purpose of this study was to evaluate functional impairment in a group of patients with bipolar disorder in remission and to determine the extent of relationships between overall functioning and current depressive, manic and panic spectrum symptoms. A subset of the patient population at the Pittsburgh site of the Systematic Treatment Enhancement Program in Bipolar Disorder (STEP-BD) study was evaluated in this study. The subsample comprises 103 male and female subjects with bipolar I disorder (n = 70), bipolar II disorder (n = 24), schizoaffective disorder - bipolar type (n = 4), or bipolar disorder NOS (n = 5). Subjects were evaluated in a period of remission (at least 4 weeks with no more than two depressive or manic symptoms). Subjects were assessed for overall functional status using the Work and Social Adjustment Scale (WSAS) and for current bipolar and panic spectrum symptoms using the Mood Spectrum Self-Report questionnaire (MOODS-SR) and Panic-Agoraphobic Spectrum Self-Report questionnaire (PAS-SR). The median WSAS total score in these remitted subjects was 14, indicating significant functional impairment. Regressing WSAS on current depressive, manic, and panic spectrum total scores, we observed a highly significant depressive spectrum effect (t = 4.9, df = 94, p < 0.0001), but non-significant panic and manic spectrum effects (t = 1.3, df = 94, p = 0.19 and t = -1.8, df = 94, p = 0.07, respectively). Bipolar disorder is associated with functional deficits even during periods of sustained and substantial remission. The degree of functional impairment is correlated with the degree of depressive spectrum symptoms.