Risk factors and outcomes of anxiety symptom trajectories in type 2 diabetes: the Fremantle Diabetes Study Phase II.

AIM: To identify determinants and outcomes of 4-year trajectories of anxiety symptoms in a community-based cohort with type 2 diabetes. METHODS: Some 1091 participants in the Fremantle Diabetes Study-Phase II with type 2 diabetes completed the Generalized Anxiety Disorder Scale at baseline and biennially for 4 years, in addition to psychological, biomedical and self-management measures. Latent growth mixture modelling identified trajectories of anxiety symptom severity, and regression models determined predictors of trajectory membership and associated outcomes. RESULTS: Two distinct groups of participants were identified: those with continuously low-no anxiety symptoms (87%) and those with improving but consistently high anxiety symptoms (elevated anxiety; 13%). Higher HbA1c and BMI, macrovascular complications and a history of generalized anxiety and/or major depressive disorder increased the risk of elevated anxiety. Elevated anxiety did not predict change in health-related outcomes over time. Elevated anxiety and depression symptoms were highly comorbid and those with both displayed the most persistent anxiety symptoms. CONCLUSIONS: A subgroup of individuals with type 2 diabetes are at risk of persistently elevated anxiety symptoms. Routine monitoring of the severity of psychological symptoms over time in this population should facilitate earlier and more intensive mood management.

Anosognosia Is Associated With Greater Caregiver Burden and Poorer Executive Function in Huntington Disease.

BACKGROUND: Anosognosia, or unawareness of one's deficits, is estimated to occur in 25% to 50% of Huntington disease (HD). The relationship between anosognosia and increased caregiver burden found in other dementias has not been determined in HD. METHODS: Patient-caregiver dyads presenting to a statewide HD clinic were assessed using the Anosognosia Scale and grouped into "anosognosia" and "no anosognosia." Caregiver burden, measured by Zarit Burden Interview (ZBI) and Caregiver Burden Inventory (CBI), demographic data, and Unified Huntington's Disease Rating Scale, including Mini-Mental State Examination, Stroop, Trail Making, Verbal Fluency, and Symbol Digit Modalities Tests, were compared between groups. RESULTS: Of the 38 patients recruited, 10 (26.3%) met criteria for anosognosia. Patients with anosognosia elicited higher caregiver burden ratings on both the ZBI (mean difference 16.4 [12.1], P < .001) and CBI (16.7 [15.0], P < .005) while also demonstrating poorer executive function. Except for CAG burden score, between-group characteristics did not differ significantly. Stroop Interference predicted both anosognosia and caregiver burden. CONCLUSIONS: In HD, anosognosia is associated with greater caregiver burden and executive deficits. Its occurrence should prompt further patient assessment and increased caregiver support.

Clinical risk factors for depressive syndrome in Type 2 diabetes: the Fremantle Diabetes Study.

AIMS: To identify early clinical predictors of depressive syndrome in people with Type 2 diabetes. METHODS: Depressive syndrome was assessed in 325 individuals with Type 2 diabetes 15 years after a baseline assessment, which included information on antidepressant use and depressive symptoms obtained using a quality-of-life scale. Follow-up current and lifetime depressive syndrome were assessed using the nine-item Patient Health Questionnaire and the Brief Lifetime Depression Scale and taking account of antidepressant use. Analyses were conducted inclusive and exclusive of antidepressant use where Patient Health Questionnaire criteria were not met. RESULTS: At baseline, the participants were aged 57.2±9.3 years and the median (interquartile range) diabetes duration was 2.2 (0.6-6.0) years. After a mean of 14.7±1.1 years' follow-up, 81 participants (24.9%) had depressive syndrome (14.8% defined by the Patient Health Questionnaire, 10.2% defined by antidepressants) and 31.4% reported lifetime depression, and in 10.2% of participants this preceded diabetes onset. With logistic regression (inclusive of antidepressants), follow-up depressive syndrome was negatively associated with education level [odds ratio 0.39 (95% CI 0.20-0.75)] and antidepressant use [odds ratio 0.11 (95% CI 0.03-0.36)] and was positively associated with depression history before diabetes onset [odds ratio 2.79 (95% CI 1.24-6.27)]. In the model exclusive of antidepressants, depressive syndrome was positively associated with baseline depressive symptoms [odds ratio 2.57 (95% CI 1.32-5.03)] and antidepressant use [odds ratio 3.54 (95% CI 1.20-10.42)] and was negatively associated with education level [odds ratio 0.39 (95% CI 0.19-0.81)]. CONCLUSIONS: Risk factors for depressive syndrome can be identified early after the onset of Type 2 diabetes. The early presence of depressive symptoms or its treatment and/or history of depression are likely indicators of vulnerability. Early risk stratification for late depressive syndrome is feasible in people with Type 2 diabetes and could assist with depression treatment or prevention.

Depression symptoms are persistent in Type 2 diabetes: risk factors and outcomes of 5-year depression trajectories using latent class growth analysis.

AIMS: To describe the long-term trajectories of depression symptom severity in people with Type 2 diabetes, and to identify predictors and associates of these trajectories. METHODS: A community-dwelling cohort of 1201 individuals with Type 2 diabetes from the Fremantle Diabetes Study Phase II was followed for 5 years. The nine-item version of the Patient Health Questionnaire was administered annually to assess depression symptoms, and biomedical and psychosocial measures were assessed at baseline and biennially. Latent class growth analysis was used to identify classes of depression severity trajectories and associated outcomes, and logistic regression models were used to determine predictors of class membership. RESULTS: Three trajectories of depression symptoms were identified: continuously low depression symptoms (85.2%); gradually worsening symptoms that then began to improve (persistent depression - low-start; 7.3%); and gradually improving symptoms which later worsened (persistent depression - high-start; 7.5%). Younger age, being a woman, and a lifetime history of major depressive disorder, were associated with greater risk of persistent depression symptoms. Persistent depression was associated with consistently higher BMI over time, but not with changes in HbA1c or self-monitoring of blood glucose. CONCLUSIONS: A subset of individuals with Type 2 diabetes is at risk of depression symptoms that remain elevated over time. Younger, overweight individuals with a history of depression may benefit from early and intensive depression management and ongoing follow-up as part of routine Type 2 diabetes care.

Lifetime depression and anxiety increase prevalent psychological symptoms and worsen glycemic control in type 2 diabetes: The Fremantle Diabetes Study Phase II.

AIMS: To determine the contribution of lifetime major depressive disorder (L-MDD) and lifetime generalized anxiety disorder (L-GAD) to current psychological symptom severity, health behaviour and glycaemic control in type 2 diabetes. METHODS: 1285 community-dwelling people with type 2 diabetes (Fremantle Diabetes Study Phase-II; FDS2) completed the PHQ-9 and Brief Life-Time Depression Scale (BLDS) to assess current and past MDD. The Generalized Anxiety Disorder Scale (GADS) and the Generalized Anxiety Disorder Scale-Lifetime (GAD-LT), designed for FDS2, assessed current and past anxiety. Data were analysed using analysis of covariance and multiple mediation models, controlling for age, gender, marital status, and diabetes duration. RESULTS: L-MDD and L-GAD were independently associated with more severe current depression (both P<0.001) and anxiety (both P<0.001) symptoms. Mediation models revealed that, through increasing the severity of current depressive symptoms, L-MDD was associated with higher HbA1c and body mass index (BMI), greater likelihood of current smoking, and reduced self-monitoring of blood glucose (SMBG) (indirect regression path ab, all P<0.001). In combination, L-MDD+L-GAD additionally elevated the risk of higher HbA1c and worse diabetes management, by increasing the severity of current depressive symptoms (indirect regression path ab, all P<0.001). CONCLUSIONS: Lifetime depression and anxiety increase risk of more severe psychological symptoms, hyperglycaemia, and difficulties with health behaviour in type 2 diabetes. Early screening for these disorders at diabetes diagnosis may be warranted to maximize long-term health outcomes.

The 'Preliminary Discourse' to Methodical Nosology, by François Boissier de Sauvages (1772).

The eighteenth century witnessed an intense drive to classify diseases as natural kinds. Together with Linné, Macbride, Cullen, Sagar and Vogel, François Boissier de Sauvages, Professor of Medicine at Montpellier, was an important player in this process. In his monumental Nosologie Méthodique, Sauvages based his nosological system on the more botanico view proposed by Thomas Sydenham, namely, that human diseases (including mental ailments) should be classified in the same way as were plants. Classic Text No. 104 is an abridged translation of the Preliminary Discourse to the Nosologie Méthodique.

Risk of suicide in Australian adults with diabetes: the Fremantle Diabetes Study.

Type 1 diabetes is associated with increased suicide risk. Data for older diabetic individuals are inconsistent. In longitudinal data from 1413 adults recruited to the Fremantle Diabetes Study from 1993-1996 and 5660 matched non-diabetic residents, followed to end-2012, the age and sex-adjusted sub-hazard ratio (95% confidence interval) for suicide in diabetic versus non-diabetic individuals was 1.16 (0.38-3.51). Older Australians with diabetes are not at increased suicide risk.

Factor analysis of the Hamilton Depression Rating Scale in Parkinson's disease.

INTRODUCTION: Several studies have validated the Hamilton Depression Rating Scale (HAMD) in patients with Parkinson's disease (PD), and reported adequate reliability and construct validity. However, the factorial validity of the HAMD has not yet been investigated. The aim of our analysis was to explore the factor structure of the HAMD in a large sample of PD patients. METHODS: A principal component analysis of the 17-item HAMD was performed on data of 341 PD patients, available from a previous cross sectional study on anxiety. An eigenvalue ≥1 was used to determine the number of factors. Factor loadings ≥0.4 in combination with oblique rotations were used to identify which variables made up the factors. Kaiser-Meyer-Olkin measure (KMO), Cronbach's alpha, Bartlett's test, communality, percentage of non-redundant residuals and the component correlation matrix were computed to assess factor validity. RESULTS: KMO verified the sample's adequacy for factor analysis and Cronbach's alpha indicated a good internal consistency of the total scale. Six factors had eigenvalues ≥1 and together explained 59.19% of the variance. The number of items per factor varied from 1 to 6. Inter-item correlations within each component were low. There was a high percentage of non-redundant residuals and low communality. CONCLUSION: This analysis demonstrates that the factorial validity of the HAMD in PD is unsatisfactory. This implies that the scale is not appropriate for studying specific symptom domains of depression based on factorial structure in a PD population.

Anxiety and motor fluctuations in Parkinson's disease: a cross-sectional observational study.

BACKGROUND: Some studies have suggested a relationship between anxiety and motor fluctuations in patients with Parkinson's disease (PD). AIM: To describe the nature of the relationship between anxiety symptoms and motor fluctuations and to describe the anxiety symptoms encountered during 'off', 'on' and 'on with dyskinesia' phases. DESIGN AND METHODS: In this cross-sectional study, 250 patients with idiopathic PD, of whom 118 had motor fluctuations, underwent a standardized clinical assessment including the Unified Parkinson's Disease Rating Scale (UPDRS), the DSM IV criteria for major depression and anxiety disorders, the Hamilton Depression Rating Scale (HAMD), and the Hamilton Anxiety Rating Scale (HARS). In addition, patients with motor fluctuations were administered a questionnaire to assess the presence of anxiety symptoms and their relation to motor states. RESULTS: Patients with motor fluctuations suffer from generalized anxiety disorder more often than patients without motor fluctuations. When patients with motor fluctuations have anxiety symptoms, the majority report that these have no temporal relationship with specific motor states. When there was a relationship, symptoms were almost always related to 'off' periods. However, a minority of patients experience anxiety symptoms during 'on' or "on with dyskinesia" periods exclusively. CONCLUSION: Our findings suggest that the relationship between anxiety and motor fluctuations is more complex than can be explained solely by 'wearing off' phenomena of levodopa. Further studies investigating the temporal dynamics of anxiety and motor fluctuations are needed.

The nosological position of apathy in clinical practice.

Apathy is increasingly recognised as a common behavioural syndrome in psychiatric disorders, but it is conceptually ill defined. The aim of this study was to examine the concept of apathy as it is currently used in neurology and psychiatry, by review of the literature and conceptual analysis. There is no consensus on diagnostic criteria for apathy as a syndrome. Apathy is mostly defined as a disorder of motivation, and operationalised as diminished goal oriented behaviour and cognition. There is discussion about whether an emotional dimension should form part of the definition of apathy. Abulia is considered a more severe type of apathy, but its nosological position is still unclear. A structured clinical interview and a proposal for diagnostic criteria for apathy in dementia have been recently validated. There are several valid and reliable scales to measure the severity of apathy in patients with psychiatric and neurological disorders. In summary, apathy is increasingly recognised as a common behavioural syndrome associated with neuropsychiatric disorders. There is a need for consensus on diagnostic criteria to facilitate future research. From a nosological perspective, future studies should examine the overlap with other psychiatric and neurodegenerative conditions and further validate specific diagnostic and assessment tools.

Predictors of cognitive impairment and dementia in older people with diabetes.

AIMS/HYPOTHESIS: Diabetes is associated with an increased risk of dementia but the reasons for this association are unclear because there are many potential mechanisms. We explored the relative contribution of diabetes-related variables as predictors of dementia in older individuals with diabetes. METHODS: Survivors, aged > or =70 or more, were recruited from an existing observational cohort study 7.6 +/- 1.0 years after baseline, when they underwent a comprehensive assessment of diabetes, complications and cardiovascular risk factors. Dementia, probable Alzheimer's disease and cognitive impairment without dementia were diagnosed clinically. Logistic regression modelling determined independent predictors of cognitive diagnoses. RESULTS: Of 302 participants, aged 75.7 +/- 4.6 years, 28 (9.3%) had dementia (16 with probable Alzheimer's disease) and 60 (19.9%) had cognitive impairment without dementia. The major independent longitudinal predictors of dementia were older age (per decade; odds ratio 4.0, 95% CI 1.59-10.10), diabetes duration (for each 5 years; odds ratio 1.69, 95% CI 1.24-2.32), peripheral arterial disease (odds ratio 5.35, 95% CI 2.08-13.72) and exercise (which was protective; odds ratio 0.26, 95% CI 0.09-0.73). For Alzheimer's disease, diabetes duration was an independent predictor in addition to age and diastolic blood pressure. The results of the cross-sectional analyses were similar with respect to diabetes duration and peripheral arterial disease. CONCLUSIONS/INTERPRETATION: Peripheral arterial disease is a strong independent risk factor for dementia in diabetes. After adjustment for a wide range of potential risk factors, diabetes duration remains independently associated with dementia and probable Alzheimer's disease, indicating that factors not measured in this study may be important in the pathogenesis of dementia in diabetes.

Insight and danger in Alzheimer's disease.

To determine the frequency, and demographic and clinical correlates of dangerous behaviours in Alzheimer's disease (AD). We assessed a consecutive series of 278 patients with AD and 45 age-comparable healthy controls with a comprehensive psychiatric and neuropsychological evaluation. Caregivers rated the frequency of patients' exposure to dangerous situations or commission of dangerous behaviours. The frequency of dangerous behaviours was 16% in the AD group and 2% in the healthy control group. The presence of anosognosia was associated with a threefold increase in the risk of dangerous behaviours, but there was no significant association between dangerous behaviours and patients' age, years of education, diagnosis of major or minor depression and presence of suicide ideation. Sixteen per cent of a consecutive series of patients with AD had dangerous behaviours during the month preceding the clinical evaluation. Anosognosia was the main clinical correlate of dangerous behaviours in this population.

Vascular depression in older people with diabetes.

AIMS/HYPOTHESIS: Cerebrovascular disease may be causal or a vulnerability factor in late-onset depression and may explain the high rate of depression in older adults with diabetes. We explored a wide range of potential explanatory variables of depression in a longitudinal study of older diabetic subjects to investigate the vascular depression hypothesis in these patients. METHODS: We recruited 207 subjects with diabetes selected for potential cognitive deficits from an existing observational cohort study (average age 75.7 +/- 4.6 years, 52.2% men) for an assessment of depression using a standardised diagnostic instrument (Cambridge Examination for Mental Disorders of the Elderly -- Revised). All subjects underwent a detailed clinical assessment at baseline and at follow-up (after 7.5 +/- 1.1 years). RESULTS: Major depression was present in 45 subjects (21.7%) and minor depression in ten (4.8%). A positive history of strokes and the presence of peripheral arterial disease were significantly associated with depression at the time of diagnosis. In a subsample of 93 cases who underwent structural neuroimaging, the presence of cerebral infarcts was also significantly associated with depression. Treatment with glucose-lowering therapy, higher serum cholesterol levels and difficulties with activities of daily living at baseline were significant predictors of depression at follow-up. CONCLUSIONS/INTERPRETATION: A history of cerebrovascular disease was strongly associated with depression and cerebrovascular risk factors were significant predictors of depression in older diabetic patients. Our findings are consistent with the hypothesis that the excess risk of depression in older diabetic patients is related to underlying cerebrovascular disease.

A diagnostic formulation for anosognosia in Alzheimer's disease.

OBJECTIVE: To determine the earliest symptoms of anosognosia in people with Alzheimer's disease and to validate a criteria-guided strategy to diagnose anosognosia in dementia. METHODS: A consecutive series of 750 patients with very mild or probable Alzheimer's disease attending a memory clinic, as well as their respective care givers, was assessed using a comprehensive psychiatric evaluation. RESULTS: The factors of anosognosia for (1) basic activities of daily living (bADL), (2) instrumental activities of daily living (iADL), (3) depression and (4) disinhibition were produced by a principal component analysis on the differential scores (ie, caregiver score minus patient score) on the anosognosia questionnaire for dementia. A discrepancy of two or more points in the anosognosia-iADL factor was found to have a high sensitivity and specificity to identify clinically diagnosed anosognosia in people with Alzheimer's disease. By logistic regression analysis, the severity of dementia and apathy were both shown to be noticeably associated with anosognosia in people with Alzheimer's disease. CONCLUSION: Anosognosia in those with Alzheimer's disease is manifested as poor awareness of deficits in iADL and bADL, depressive changes and behavioural disinhibition. The frequency of anosognosia is found to increase considerably with the severity of dementia. The validity of a specific set of criteria to diagnose anosognosia in people with Alzheimer's disease was shown, which may contribute to the early identification of this condition.

A prospective longitudinal study of apathy in Alzheimer's disease.

BACKGROUND: Apathy and depression are the most frequent behavioural and psychiatric disorders in Alzheimer's disease, and may both have a negative impact on the progression of the illness. OBJECTIVES: To examine the clinical correlates of apathy in Alzheimer's disease (AD), and to determine whether apathy is a significant predictor of more rapid cognitive, functional and emotional decline. METHODS: Using a structured psychiatric evaluation, we examined a consecutive series of 354 subjects meeting clinical criteria for AD. Apathy was assessed by the Apathy Scale, and diagnosed using standardised criteria. Additional measurements included scales for depression, functional impairment, and global cognitive functions. A follow up evaluation was carried out in 247 patients (70% of the total sample) between 1 and 4 years after the baseline evaluation. RESULTS: Apathy was significantly associated with older age (p = 0.009), and a higher frequency of minor and major depression (p < 0.0001). Apathy at baseline was a significant predictor of depression at follow up (p = 0.01), and was associated with a faster cognitive (p = 0.0007) and functional decline (p = 0.006). CONCLUSIONS: Apathy in AD is a behavioural marker of a more aggressive dementia, characterised by a faster progression of cognitive, functional, and emotional impairment.

A prospective study of depression and mortality in patients with type 2 diabetes: the Fremantle Diabetes Study.

AIMS/HYPOTHESIS: Depression is associated with excess mortality in patients with type 2 diabetes. We investigated the impact, and possible causal mechanisms, of depression on all-cause and cardiac mortality in patients with type 2 diabetes. METHODS: We recruited 1,273 patients with type 2 diabetes from a postcode-defined community (average age 64.1+/-11.2 years, 48.7% males, median duration of diabetes 4 years [range 1.0-9.0]) and followed them for 7.8+/-2.4 years. Depression was assessed using data obtained using a quality-of-life questionnaire, and cause and date of death were obtained from the state registry. RESULTS: Depression was present in 31.5% of subjects at recruitment. Depressed subjects had a longer duration of diabetes, more cardiovascular risk factors, CHD, cerebrovascular disease and diabetic microvascular complications at baseline, and higher all-cause and cardiac mortality rates during follow-up. In Cox proportional hazards models and after adjustment for demographic and diabetes-related variables and cardiovascular risk factors, depression was significantly associated with excess all-cause and cardiac mortality. When diabetic microvascular and macrovascular complications were added to the Cox models, depression was not significantly associated with excess all-cause or cardiac mortality. CONCLUSIONS/INTERPRETATION: Depression in patients with type 2 diabetes is associated with a greater prevalence of complications but is not an independent predictor of all-cause or cardiac mortality. Depression may contribute to the progression of important prognostic variables in diabetes, particularly macrovascular and microvascular disease.

On the overlap between apathy and depression in dementia.

BACKGROUND: Whereas apathy is increasingly recognised as a frequent abnormal behaviour in dementia, its overlap with depression remains poorly understood. AIMS: To assess the psychometric characteristics of a structured interview for apathy, and to examine the overlap between apathy and depression in dementia. METHODS: A total of 150 patients with Alzheimer's disease (AD) underwent a comprehensive psychiatric and cognitive assessment. RESULTS: Twelve per cent of the sample met criteria for both apathy and depression, 7% met criteria for apathy only, and 31% met criteria for depression only. Apathy (but not depression) was significantly associated with more severe cognitive deficits. Apathy and anxiety scores accounted for 65% of the variance of depression scores in dementia, and the diagnosis of apathy had a minor impact on the rating of severity of depression. CONCLUSIONS: The Structured Interview for Apathy demonstrated adequate psychometric characteristics. Using a novel structured interview for apathy in AD we demonstrated that whereas the construct of depression primarily consists of symptom clusters of apathy and anxiety, apathy is a behavioural dimension independent of depression.

White matter hyperintensities are significantly associated with cortical atrophy in Alzheimer's disease.

BACKGROUND AND OBJECTIVE: Methodological variability in the assessment of white matter hyperintensities (WMH) in dementia may explain inconsistent reports of its prevalence and impact on cognition. We used a method of brain MRI segmentation for quantifying both tissue and WMH volumes in Alzheimer's disease (AD) and examined the association between WMH and structural and cognitive variables. METHODS: A consecutive series of 81 patients meeting NINCDS-ADRDA criteria for probable AD was studied. Nineteen healthy volunteers of comparable age served as the control group. Patients had a complete neurological and neuropsychological evaluation, and a three dimensional MRI was obtained. Images were segmented into grey matter, white matter, and cerebrospinal fluid. WMH were edited on segmented images, and lobar assignments were based on Talairach coordinates. RESULTS: Mild and moderate to severe AD patients had significantly more WMH than controls (p<0.05). WMH preferentially involved the frontal lobes (70%), were inversely correlated with grey matter cortical volume (R(2) = 0.23, p<0.001), and were significantly associated with vascular risk factors and with a worse performance on memory tasks. CONCLUSION: Objective measurements of tissue volumes in AD demonstrated that WMH are significantly related to cortical atrophy and neuropsychological impairment.

Theory of mind and pragmatic abilities in dementia.

OBJECTIVE: "Theory of Mind" (ToM) is the capacity to attribute mental states to oneself and to others and to interpret behavior in terms of mental states. Deficits in both ToM and pragmatic abilities have been described in patients with neurologic disorders, such as frontal lobe lesions and right hemisphere strokes, but have not been assessed in demented patients. METHODS: This study examined ToM and pragmatic abilities in a consecutive series of 34 patients with probable Alzheimer disease (AD) using a second-order false belief story, 11 short stories assessing understanding of social situations, and a test of pragmatic abilities assessing both indirect requests and-conversational implications. RESULTS: Sixty-five percent of AD patients with mild dementia could not pass a second-order false belief task, whereas no failures were found in a group of 10 age-comparable healthy controls. AD patients who did not pass the second-order false belief task had more severe deficits on tests of verbal anterograde memory, verbal comprehension, abstract thinking, and naming, as compared with AD patients who passed the task. AD patients also showed significantly more severe pragmatic deficits than age-comparable healthy controls, and there was a significant association between ToM and pragmatic deficits. On the other hand, there were no significant associations between ToM or pragmatic deficits, and behavioral problems frequently reported in AD such as depression, delusions, apathy, and irritability. CONCLUSIONS: This initial exploratory investigation demonstrated significant deficits in both ToM and pragmatic abilities in a consecutive series of AD patients with mild dementia.

Prevalence and correlates of parkinsonism in patients with primary depression.

The authors examined the prevalence, clinical correlates, and longitudinal changes of parkinsonism in 94 patients with primary depression and 20 healthy control subjects. Parkinsonism was present in 20% of patients with primary depression. This syndrome was significantly associated with older age, more severe depression, and more severe cognitive impairment. In a subgroup of depressed patients, parkinsonism was reversible upon recovery from the mood disorder.