Course Of Affective Illness Research Articles

Longitudinal association between exposome score for schizophrenia and clinical features: results from the Athens First-Episode Psychosis Research Study

IntroductionPreviously, environmental vulnerability for schizophrenia assessed through exposome score for schizophrenia (ES-SCZ) was associated with the risk for psychosis development.ObjectivesThe current study aims to investigate the longitudinal association between ES-SCZ and symptom severity in individuals with first episode psychosis (FEP) to understand how environmental exposures affect illness course.MethodsBaseline and 1-month follow-up assessments were available for 225 individuals with FEP from the Athens FEP Research Study. The Positive and Negative Syndrome Scale (PANSS) was used to measure clinical features. In accordance with previous reports, the ES-SCZ was calculated by summing log-odds weighted environmental exposures (childhood adversities, winter birth, and cannabis use). To model the course of clinical features over time the effects of the ES-SCZ-by-time interaction, ES-SCZ, and time were analyzed with multilevel regression analyses. Age, sex, and education were added as covariatesResultsThe analyses of change of PANSS total score over time indicated that clinical features decreased from baseline to the 1-month follow-up assessment. The association between ES-SCZ and PANSS total score were not statistically significant. The analyses of the PANSS total score over time indicated an ES-SCZ-by-time interaction (B = 2.82 [95% CI 0.28; 5.35], P-value = 0.029), meaning the decrease of the PANSS total score over time were dependent on ES-SCZ and individuals with high ES-SCZ showed less improvementConclusionsThe findings show that the total environmental predisposition to schizophrenia (ES-SCZ) not only increases the risk for psychosis development but may also influences the illness course.DisclosureNo significant relationships.

P507. Longitudinal Association Between Exposome Score for Schizophrenia and Clinical Features: Results From the Athens First-Episode Psychosis Research Study

Previously, environmental vulnerability for schizophrenia assessed through exposome score for schizophrenia (ES-SCZ) was associated with the risk for psychosis development. The current study aims to investigate the longitudinal association between ES-SCZ and symptom severity in individuals with first-episode psychosis (FEP) to understand how environmental exposures affect illness course.

Treating patients with severe mental illness with narrative exposure therapy for comorbid post-traumatic stress disorder.

Interpersonal trauma and post-traumatic stress disorder (PTSD) in patients with severe mental illness (SMI) negatively affect illness course. Narrative exposure therapy (NET) is effective in vulnerable patient groups, but its efficacy and applicability has not been studied in out-patients with SMI. We aimed to evaluate the efficacy and applicability of NET in SMI on changes in PTSD, dissociation, SMI symptoms, care needs, quality of life, global functioning and care consumption. The study had a single-group, pre-test-post-test, repeated-measures design and was registered in The Netherlands National Trial Register (identifier TR571). Primary outcomes were assessed at pre-treatment (T0), 1 month post-treatment (T1) and 7 months' follow-up (T2), with a structured interview for PTSD and dissociation screening. Secondary outcomes followed routinely SMI measurements and medical data. Mixed models were used for data analysis. The majority of the 23 participants was female (82%). Mean age was 49.9 years (s.d. 9.8) and mean PTSD duration was 24.1 years (s.d. 14.5). Mean PTSD severity decreased from 37.9 at T0 to 31.9 at T1 (-6.0 difference, 95%CI -10.0 to -2.0), and decreased further to 24.5 at T2 (-13.4 difference, 95%CI -17.4 to -9.4). Dissociation, SMI symptoms, duration of contacts, and medication decreased; global functioning increased; and quality of life and perceived needs did not change. Eleven participants were in remission for PTSD at T2, of which five were also in remission for major depression. NET appeared efficacious and applicable to out-patients with SMI and PTSD, and was well tolerated.

Adiponectin is decreased in bipolar depression

Objectives: Bipolar disorder (BD) is often accompanied by medical comorbidities, which affect illness course and prognosis. Adipokines may not only be involved in the aetiopathogenetic mechanisms of these comorbidities; there might be an association between adipokines and the neuropsychiatric core features of BD such as mood disturbances and cognitive deficits.Methods: In this investigation, fasting blood samples from 120 individuals with BD (75 euthymic and 45 with mild depressive symptoms) and 68 control subjects were taken and adiponectin and leptin concentrations were analysed.Results: We found that, in female participants, adiponectin levels differed significantly between patients and controls indicating lower levels in individuals with BD, even after controlling for BMI (F(1,92) = 4.65, P = 0.034, partial η2 = 0.05). After stratification by mood status we found a significant difference in adiponectin between controls, euthymic and depressive patients (F(2, 180) = 4.90, P = 0.008, partial η2 = 0.05).Conclusions: This investigation confirms previous findings of an association between low adiponectin levels and depressive state in individuals with BD. Beyond its immediate effect on central nervous system function, adiponectin might interfere with pathophysiological mechanisms of BD and its somatic comorbidities via involvement in metabolic and inflammatory processes.

The relationship between sleep-wake cycle and cognitive functioning in young people with affective disorders.

Although early-stage affective disorders are associated with both cognitive dysfunction and sleep-wake disruptions, relationships between these factors have not been specifically examined in young adults. Sleep and circadian rhythm disturbances in those with affective disorders are considerably heterogeneous, and may not relate to cognitive dysfunction in a simple linear fashion. This study aimed to characterise profiles of sleep and circadian disturbance in young people with affective disorders and examine associations between these profiles and cognitive performance. Actigraphy monitoring was completed in 152 young people (16–30 years; 66% female) with primary diagnoses of affective disorders, and 69 healthy controls (18–30 years; 57% female). Patients also underwent detailed neuropsychological assessment. Actigraphy data were processed to estimate both sleep and circadian parameters. Overall neuropsychological performance in patients was poor on tasks relating to mental flexibility and visual memory. Two hierarchical cluster analyses identified three distinct patient groups based on sleep variables and three based on circadian variables. Sleep clusters included a ‘long sleep’ cluster, a ‘disrupted sleep’ cluster, and a ‘delayed and disrupted sleep’ cluster. Circadian clusters included a ‘strong circadian’ cluster, a ‘weak circadian’ cluster, and a ‘delayed circadian’ cluster. Medication use differed between clusters. The ‘long sleep’ cluster displayed significantly worse visual memory performance compared to the ‘disrupted sleep’ cluster. No other cognitive functions differed between clusters. These results highlight the heterogeneity of sleep and circadian profiles in young people with affective disorders, and provide preliminary evidence in support of a relationship between sleep and visual memory, which may be mediated by use of antipsychotic medication. These findings have implications for the personalisation of treatments and improvement of functioning in young adults early in the course of affective illness.

Evidence for accelerated vascular aging in bipolar disorder

ObjectivePersons with bipolar disorder face excess risk of cardiovascular disease, although the biobehavioral mechanisms and time course are unclear. We measured vascular stiffness in a cross-sectional sample of participants with bipolar disorder and compared results to published normative data to assess time-course and relationship to behavioral risk factors. Methods62 individuals with bipolar disorder (33±6.7years; 64% female) underwent non-invasive assessment of arterial stiffness through arterial applanation tonometry. Lifetime tobacco exposure was estimated on clinical interview. Physical activity was assessed using the long-version of the International Physical Activity Questionnaire (IPAQ). A food frequency questionnaire was used to compute Alternate Healthy Eating Index (AHEI), a measure of overall dietary quality. Medication histories were systematically abstracted from pharmacy records. ResultsParticipants over the age of 32 (median split) had greater arterial stiffness than expected from age-based population norms for pulse wave velocity (PWV) (7.6 vs. 7.0m/s, p=.02) and estimated aortic augmentation pressure (AIx) (14.2 vs. 8.2%, p=.0002). The younger portion of the sample did not differ from population norms on these measures (PWV 6.3 vs. 6.4m/s, p=.45 and AIx 7.6 vs. 7.4%, p=.60). In the older half of the sample, physical activity was inversely associated with AIx and poorer diet marginally associated with PWV. These findings were independent of body mass index (BMI), which was strongly related to arterial stiffness. ConclusionRisk for vascular disease may be acquired over the long-term course of affective illness. This risk appears to reflect maladaptive health behaviors, which may be amenable to intervention.

Frontal lobe changes occur early in the course of affective disorders in young people

BackgroundMore severe and persistent forms of affective disorders are accompanied by grey matter loss in key frontal and temporal structures. It is unclear whether such changes precede the onset of illness, occur early in the course or develop gradually with persistence or recurrence of illness. A total of 47 young people presenting with admixtures of depressive and psychotic symptoms were recruited from specialist early intervention services along with 33 age matched healthy control subjects. All participants underwent magnetic resonance imaging and patients were rated clinically as to current stage of illness. Twenty-three patients were identified as being at an early 'attenuated syndrome' stage, while the remaining were rated as having already reached the 'discrete disorder' or 'persistent or recurrent illness' stage. Contrasts were carried out between controls subjects and patients cohorts with attenuated syndromes and discrete disorders, separately.ResultsThe patients that were identified as having a discrete or persisting disorder demonstrated decreased grey matter volumes within distributed frontal brain regions when contrasted to both the control subjects as well as those patients in the attenuated syndrome stage. Overall, patients who were diagnosed as more advanced in terms of the clinical stage of their illness, exhibited the greatest grey matter volume loss of all groups.ConclusionsThis study suggests that, in terms of frontal grey matter changes, a major transition point may occur in the course of affective illness between early attenuated syndromes and later discrete illness stages.

Cholesterol and affective morbidity

Depression and mania have been linked with low cholesterol though there has been limited prospective study of cholesterol and subsequent course of affective illness. We studied the relationship between fasting total cholesterol and subsequent depressive and manic symptoms. A total of 131 participants from a prospective cohort study were identified as having had a fasting total cholesterol evaluation at intake. Participants were predominantly inpatients at index visit and were followed for a median of 20 and up to 25 years. Cholesterol was modeled with age, gender, and index use of a mood stabilizer in linear regression to assess its influence on subsequent depressive symptom burden in participants with unipolar disorder as well as depressive and manic symptom burden in participants with bipolar disorder. Among bipolar participants ( N = 65), low cholesterol predicted a higher proportion of follow-up weeks with manic, but not depressive symptoms. Cholesterol did not appear to predict depressive symptom burden among participants with unipolar depression ( N = 66). Lower cholesterol levels may predispose individuals with bipolar disorder to a greater burden of manic symptomatology and may provide some insight into the underlying neurobiology.

Patterns of sensitisation in the course of affective illness: A life-charting study of treatment-refractory depressed patients

Background: A ‘sensitisation’ process over time has been suggested by Post and collaborators — the affective illness course shows a tendency towards more frequent, deeper, and less stress-related episodes over time. The main aim of the present study was to test the sensitisation hypothesis using a Swedish Life Charting program. Methods: Thirty patients with treatment-refractory affective disorder, of whom four had bipolar I disorder, were first interviewed using a semistructural interview manual covering episodes, treatment and stress. All previous psychiatric records were then recruited. Information from the records and from the interview was coalesced into individual, retrospective life charts. Results: Twenty patients showed a sensitisation course and 10 patients showed a non-sensitisation course. In both groups, almost 90% of illness episodes had undergone treatment. Time spent in illness since onset of the affective disorder was about 33% for the sensitisation group and more than 50% for the non-sensitisation group. Limitations: The retrospective nature of the study is a limitation. The results apply to patients with severe treatment-refractory affective disorder and may not be generalisable to general patients with less-severe mood disorders. Conclusions: Our results partially validate the Post hypothesis of affective sensitisation in demonstrating this phenomenon in more than half of our affectively recurring patients. However, a substantial minority were clearly non-sensitisers showing a stable but more malignant illness course. Future studies need to elucidate whether these two groups benefit from different kinds of treatment.

Serotonin transporter promoter genotype and illness recurrence in mood disorders

We tested the hypothesis that allelic variation of 5-HTT linked polymorphic region (5-HTTLPR) could influence illness onset and recurrence in 129 bipolar and 128 unipolar recurrent patients. Among bipolar patients, homozygotes for the short variant showed an earlier age at onset and a lower recurrence rate than heterozygotes and homozygotes for the long variant. Unipolar patients showed a trend toward the same difference. Data support a role for 5-HTTLPR in course of affective illness.

Predictors of recurrence in affective disorder — analyses accounting for individual heterogeneity

Background: Previous studies suggest that gender, age at onset, and marital status act as risk factors for further recurrence initially during the course of affective disorder but not at a later stage. These studies did, however, not take the individual liability to recurrence into account. Method: The effect of predictors of recurrence was estimated with the use of generalised linear mixed models in a case register study including a random sample of all patients admitted with primary affective disorder in Denmark during 1971–1993. Results: In total, 7047 first admission patients with a diagnosis of affective disorder, depressive or manic/circular type were included in the analyses. The study confirmed that the effect of the type of disorder, age at first admission, and never being married decreased during the course of illness even when the individual liability to recurrence was taken into account. No differences in the effect of gender and in the effect of a recent divorce were found between early and later episodes and the effect of a recent death of a spouse seemed to increase during the course of illness. The risk of recurrence increased with every new episode for all sub-groups of patients. Conclusion: The effect of some, but not all, predictors of recurrence decline during the course of affective illness. The number of previous episodes predicts recurrence in most subgroups of patients. Limitation: The data relate to re-admissions rather than recurrence. Clinical relevance: The study underscores the importance of the illness process itself.

The dexamethasone/corticotropin-releasing hormone test in depression in bipolar and unipolar affective illness

The combined dexamethasone/corticotropin-releasing hormone (DEX/CRH) test was performed in forty patients with depression (12 male, 28 female), aged 20–68 years, in the course of affective illness (16 bipolar, 24 unipolar) both during acute depressive episode and in remission. The results were compared with those of 20 healthy control subjects (10 male, 10 female), aged 22–52 years. During acute depressive episode, cortisol concentration at 16 h after dexamethasone, 1.5 mg, and cortisol release after subsequent infusion of CRH, 100 μg, were significantly elevated in bipolar patients compared with unipolar ones and with control subjects. Patients with multiple episodes of unipolar depression exhibited greater cortisol levels after CRH than control subjects. In remission, significantly higher cortisol concentrations measured at 30 min–1 h after CRH infusion were found in bipolar than in unipolar patients. Male bipolar patients had significantly higher cortisol level than bipolar females before and at 1.5 h after CRH. First episode unipolar patients during remission had lower levels of cortisol than control subjects before and at 1.5 h after CRH. Correlation between the magnitude of cortisol response and age was found within unipolar depressed patients but not in bipolar ones. On the other hand, correlation of test results with intensity of depression measured by Hamilton scale as well as with insomnia and anxiety subscales was more robust in bipolar subjects than in unipolar ones. It is concluded that the dysregulation of hypothalamic-pituitary-adrenal (HPA) axis activity, detected by DEX/CRH test is significantly more marked in patients with depression in the course of bipolar affective illness than in unipolar depression. Within unipolar depression, this dysregulation may increase with the time course of the illness.

Maintenance strategies for unipolar depression: an observational study of levels of treatment and recurrence

Background: This paper analyses data from a large observational study of the course of affective illness to provide insight into the duration and dose of effective maintenance therapies. Methods: The data are 236 unipolar patients who had received antidepressants during recovery and were followed for affective recurrence for up to 5 years. Using data on the naturally selected somatic treatments, we have conducted analyses that adjust for the potential confounding effects of prognosis and treatment intensity to estimate the causal effect of level of medication on the course of recurrence. Results: The results of these analyses show that it is important for patients to remain on the level of somatotherapy used to treat the acute episode for the initial 8 months after symptoms have abated. After that time, the rate of recurrence for patients with fewer than five previous episodes is approximately 1% per week or less at all levels of medication (including discontinuation). Patients who had experienced more than several recurrences are at greater risk of recurrence and continue to benefit from any level of medication during the first year after recovery. Conclusions: The CDS analyses reported here suggest that effective maintenance strategies for all but highly recurrent patients may be a middle road, opting for full-dose strategies of limited duration. These results have implications at both the policy and the clinical level, given the need to consider both monetary and nonmonetary costs (side-effects) associated with continued pharmacotherapy during remission. Limitations: The observational design of the CDS limits the degree to which cause and effect relationships can be inferred from the observed associations.

Causal estimation of time-varying treatment effects in observational studies: application to depressive disorder.

Clinicians recognize three phases of the treatment of major depression: an acute phase to control disabling symptoms, a continuation phase to avoid relapses of a single episode, and a preventive phase to avoid recurrences of new episodes over time. With no directly measurable trace of the underlying pathological process, the distinction is based arbitrarily on the passage of time in remission. The clinician who has successfully treated a patient with antidepressant medications in the acute phase has a critical clinical decision to make for the continuation and preventive phases: whether to continue to prescribe the medication, for how long, and at what dose. This decision, like most clinical decisions in psychiatry, is not yet completely determined by the results of randomized clinical trials. Only a handful of such trials have been completed, covering just a fraction of the possible maintenance strategies (defined by treatment drop times). For many reasons, observational studies of the outcome of naturally occurring treatment choices play an important supporting role, helping to extend the reach of completed studies and to design new studies. Causal inference from observational studies has usually been considered in the context of a decision among a few fixed alternatives at a single time. The particular causal effect of interest in the maintenance of remission dictates that treatment be studied over remission time. This challenges the causal analysis of the observational study. We present issues arising from assessing temporal treatment effects due to nonrandomized treatment assignment over time. We use data from a large observational study of the course of affective illness, to illustrate an approach to this problem.

Decreased activity of erythrocyte membrane ATPases in depression and schizophrenia.

Erythrocyte ATP-ase activities were determined in 32 drug-free patients with depression in the course of affective illness, during acute episode, in 24 drug-free patients with schizophrenia, during exacerbation of the illness, and in 25 healthy control subjects. In both depression and schizophrenia, the activities of all three ATP-ases studied (Na-K ATPase, Mg ATPase, Ca-Mg ATPase) were significantly lower than in control subjects. No difference was found between patients with depression in the course of bipolar and unipolar affective illness. In patients with schizophrenia, the activity of Na-K ATPase was lower in the paranoid type of the illness. The results are discussed in the light of contemporary biochemical concepts of major psychoses.

Possible role of adenosine receptors in psychiatric diseases

AbstractEffective antidepressive treatments like electroconvulsive therapy and sleep deprivation increase adenosine A1‐receptors in the brains of experimental animals. It has therefore been of considerable interest that carbamazepine, which is known to be clinically similarly effective as lithium ions in the prophylaxis of affective illness, interacts with adenosine receptors. We have recently characterized this interaction using cellular model systems, in which adenosine receptor subtypes evoke different second messenger responses. The results show that carbamazepine at therapeutically relevant concentrations, is a selective antagonist of the A1‐ but not of the high affinity A2‐receptor subtype. The increase in the frequency and severity of the episodes that is often observed in the course of affective illness has been interpreted as the result of plastic changes in neuronal sensitivity that lead to the development of pathologically supersensitive neural circuits. The prophylactic properties of lithium ions are thought to be due to a dampening of the inositol‐phospholipid second not directly influence the generation of inositol phosphates. However, adenosine‐agonists, presumably acting via A1‐receptors, can potently modulate the neurotransmitter‐evoked increase of inositol phosphates and cytosolic free calcium ions. This effect could play a role in synaptic plasticity. Indeed, A1‐agonists can block the development of “long term potentiation,” a model of synaptic plasticity. We suggest that the prophylactic properties of carbamazepine in affective psychoses might be related to the inhibition by carbamazepine and the subsequent supersensitization of the A1‐receptors that modulate the neurotransmitter‐induced formation of inositol phosphates and synaptic plasticity. © 1993 Wiley‐Liss, Inc.

The longitudinal course of affective illness: Mathematical models involving chaos theory : Mark S. George, Mark Jones, Robert M. Post, Kristin Mikaluskas, Gabriele Leverich NIMH, Bethesda, MD 20817

The longitudinal course of affective illness: Mathematical models involving chaos theory : Mark S. George, Mark Jones, Robert M. Post, Kristin Mikaluskas, Gabriele Leverich NIMH, Bethesda, MD 20817

Sensitization, kindling, and carbamazepine: an update on their implications for the course of affective illness.

Sensitization, kindling, and carbamazepine: an update on their implications for the course of affective illness.

Major depression in patients with panic disorder: factors associated with course and recurrence

The relationship between anxiety and depressive disorders has been the subject of considerable interest and controversy. In this study, the occurence and course of affective illness was systematically examined in 63 patients meeting DSM-III-R criteria for panic disorder. Forty (63%) of the patients had experienced at least one major depressive episode. Of these, 13 (32.5%) experienced their first depressive episode prior to the onset of panic disorder, 15 (37.5%) experienced their first depressive episode after the onset of panic disorder, and in 12 (30.0%) the onset of the disorders was concurrent. Patients with agoraphobia had comparable rates of depression (68%) to patients without agoraphobia (53%, P=NS), and they had similar temporal patterns of depressive illness. Comorbidity with social phobia was associated with an increased longitudinal likelihood of major depression compared to patients without this comorbird diagnosis ( P<0.05). Patients with longer duration of illness, early onset depression, melancholic depression, or family histories of anxiety or depression had an increased likelihood of having experienced recurrent depression. These findings are discussed in the context of current theories regarding the development of affective illness in patients with anxiety disorders.

Major depression in patients with social phobia

The authors examined the longitudinal course of affective illness retrospectively in 63 patients with social phobia and 54 patients with panic disorder. Significantly fewer (35%) of the patients with social phobia than patients with panic disorder (63%) had experienced at least one major depressive episode. Patients with generalized social phobia and patients with specific social phobia had comparable past rates of major depression (37% and 30%, respectively). The clinical and theoretical implications of these findings are discussed within the context of current concepts regarding the development of depressive symptoms in patients with anxiety disorders.