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This prospective open-label feasibility study aimed to evaluate acceptability, tolerability and compliance with dietary intervention with K.Vita, a medical food containing a unique ratio of decanoic acid to octanoic acid, in individuals with drug-resistant epilepsy. Adults and children aged 3–18 years with drug-resistant epilepsy took K.Vita daily whilst limiting high-refined sugar food and beverages. K.Vita was introduced incrementally with the aim of achieving ≤35% energy requirements for children or 240 ml for adults. Primary outcome measures were assessed by study completion, participant diary, acceptability questionnaire and K.Vita intake. Reduction in seizures or paroxysmal events was a secondary outcome. 23/35 (66%) children and 18/26 (69%) adults completed the study; completion rates were higher when K.Vita was introduced more gradually. Gastrointestinal disturbances were the primary reason for discontinuation, but symptoms were similar to those reported from ketogenic diets and incidence decreased over time. At least three-quarters of participants/caregivers reported favourably on sensory attributes of K.Vita, such as taste, texture and appearance, and ease of use. Adults achieved a median intake of 240 ml K.Vita, and children 120 ml (19% daily energy). Three children and one adult had ß-hydroxybutyrate >1 mmol/l. There was 50% (95% CI 39–61%) reduction in mean frequency of seizures/events. Reduction in seizures or paroxysmal events correlated significantly with blood concentrations of medium chain fatty acids (C10 and C8) but not ß-hydroxybutyrate. K.Vita was well accepted and tolerated. Side effects were mild and resolved with dietetic support. Individuals who completed the study complied with K.Vita and additional dietary modifications. Dietary intervention had a beneficial effect on frequency of seizures or paroxysmal events, despite absent or very low levels of ketosis. We suggest that K.Vita may be valuable to those with drug-resistant epilepsy, particularly those who cannot tolerate or do not have access to ketogenic diets, and may allow for more liberal dietary intake compared to ketogenic diets, with mechanisms of action perhaps unrelated to ketosis. Further studies of effectiveness of K.Vita are warranted., See Auvin (https://doi.org/10.1093/braincomms/fcab234) for a scientific commentary on this article. Schoeler et al. report that K.Vita, a decanoic acid-rich medical food, was well-tolerated when introduced gradually and flexibly to individuals with epilepsy. Seizures or paroxysmal events reduced by 50% (95% CI 39–61%). Only 4/61 (7%) patients had ß-hydroxybutyrate levels >1 mmol/l. K.Vita may be valuable for individuals with drug-resistant epilepsy., Graphical Abstract Graphical Abstract

Despite the high frequency of depression in the first year following stroke, few studies have predicted risk of depression after the acute and subacute stroke periods. The aim of this study was to identify, in the acute and subacute periods, measures that would predict major depression during the first year after stroke.Study subjects were inpatients with ischemic stroke aged 20-85 years within 6 weeks of onset. Patients were evaluated at baseline and at 3, 6, 9, and 12 months. Patients were diagnosed with major depression using the Structured Clinical Interview for DSM-IV. The severity of depressive symptoms was measured with the Patient Health Questionnaire-9 (PHQ-9) and the Montgomery-Åsberg Depression Rating Scale (MADRS).Of the 152 potential patients who met inclusion criteria, 49 had follow-up evaluations; one patient with major depression in the acute and subacute periods was excluded from the analysis. Among the remaining 48 patients, the number of those with major depression during the first year of stroke onset was five (10.4%). Patients who developed major depression had significantly more depressive symptoms in the acute and subacute stroke phase as assessed by both the PHQ-9 and MADRS. Patients with PHQ-9 scores ≥9 in the acute and subacute stroke phases were significantly more likely to develop major depression in a chronic phase of stroke.The self-administered PHQ-9 can identify patients in the acute and subacute stroke periods who are at increased risk for developing major depression during the first year after stroke.

Objective This study re-examined patients from a 1-year randomized controlled double-blind trial of escitalopram, problem-solving therapy (PST), or placebo to prevent depression among patients less than 3 months after a stroke. The objective of the current study was to determine if preventive treatment would predict time to death over 8–10 years of follow-up. Based on the importance of depression in poststoke mortality and a previous study of this population at 18 months' follow-up showing that stopping escitalopram but not PST led to a significant increase in depression, the authors hypothesized that PST would be associated with the longest time to death. Methods Of 129 eligible patients, 122 were contacted and 7 were lost to follow-up. Families and surviving patients were interviewed to determine current health status or the date and cause of death. Results Using the Weibull model of log time (years) to death, controlled for age, severity of physical illness, gender, severity of stroke, and history of depression after study entry, there was a significant independent effect of treatment. PST significantly and independently increased the time to mortality, whereas older age and major depression significantly and independently decreased the time to death. Conclusion To the authors' knowledge, this is the first time a psychological antidepressant treatment administered for 1 year has been associated with increased survival among patients who have suffered a stroke.

Background To evaluate the efficacy of treatment with nefiracetam compared to placebo in poststroke apathy. Methods A parallel group, randomized, placebo-controlled, double-blind two-center trial in patients with recent stroke and apathy was conducted in 2 tertiary teaching hospitals in Perth, Western Australia, between March 2010 and October 2014. Consenting patients hospitalized with stroke were screened for participation at the time of hospitalization and, if diagnosed with apathy 8-36 weeks later, they were randomized to 12 weeks of 900 mg/day nefiracetam or placebo. The primary efficacy parameter was change in apathy at 12 weeks defined by the 14-item Apathy Scale (AS). Results Of 2514 patients screened, only 377 (15%) were eligible for the study after the first screening, 233 declined further participation, and 144 were assessed for apathy at 8-36 weeks post stroke to confirm eligibility. Twenty patients out of 106 with a complete psychiatric assessment had apathy (19%). Of this sample, 13 patients were randomized. Overall, the AS score decreased by a mean of 7.0 points (95% CI = −14.6 to .6), but there was no significant between-group difference at week 12 (mean paired t -tests, P > .14). Conclusions Treatment with nefiracetam did not prove to be more efficacious than placebo in ameliorating apathy in stroke. The main limitation was the very small sample randomized, highlighting the limitations of conducting drug trials for behavioral problems among stroke patients. Pharmacological studies of apathy in stroke will require a large multicenter study and a massive sample of patients.

Poststroke depression (PSD) has been recognized by psychiatrists for more than 100 years, but controlled systematic studies did not begin until the 1970s. Meta-analyses addressing almost all major clinical issues in the field have emerged because of the relatively small number of patients included in some stroke studies. In order to build large databases, these meta-analyses have merged patients with rigorously assessed mood disorders with major depressive features with patients scoring above arbitrary cutoff points on depression rating scales, thus missing important findings such as cognitive impairment associated with major but not minor depression. Nevertheless, PSD occurs in a significant number of patients and constitutes an important complication of stroke, leading to greater disability as well as increased mortality. The most clinically important advances, however, have been in the treatment and prevention of PSD. Recent meta-analyses of randomized controlled trials for the treatment of PSD have demonstrated the efficacy of antidepressants. Similarly, randomized controlled trials for prevention of PSD have shown that antidepressants significantly decrease the incidence of PSD compared with placebo. Early antidepressant treatment of PSD appears to enhance both physical and cognitive recovery from stroke and might increase survival up to 10 years following stroke. There has also been progress in understanding the pathophysiology of PSD. Inflammatory processes might be associated with the onset of at least some depressive symptoms. In addition, genetic and epigenetic variations, white matter disease, cerebrovascular deregulation, altered neuroplasticity, and changes in glutamate neurotransmission might be relevant etiological factors. Further elucidation of the mechanism of PSD may ultimately lead to specific targeted treatments.

Background The objective of this study was to evaluate citalopram for executive functioning in Huntington's disease (HD). Methods The study was randomized, double-blind, and placebo-controlled. Thirty-three adults with HD, cognitive complaints, and no depression (Hamilton Depression [HAM-D] rating scale ≤12) were administered citalopram 20 mg or placebo (7 visits, 20 weeks), with practice and placebo run-ins. The primary outcome was change in executive functioning. Results The intent to treat analysis was controlled for practice effects, comparing visits 1 and 2 to visits 5 and 6 for citalopram versus placebo. There were no significant benefits on the executive function composite (treatment-placebo mean difference −0.167; 95% confidence interval [CI], −0.361 to 0.028; P = .092). Citalopram participants showed improved clinician-rated depression symptoms on the HAM-D (t = −2.02; P = 0.05). There were no group differences on motor ratings, self-reported executive functions, psychiatric symptoms, or functional status. Conclusions There was no evidence that short-term treatment with citalopram improved executive functions in HD. Despite excluding patients with active depression, participants on citalopram showed improved mood, raising the possibility of efficacy for subsyndromal depression in HD. © 2013 International Parkinson and Movement Disorder Society

Objective Apathy occurs frequently following stroke and prior studies have demonstrated the negative effect of apathy on recovery from stroke. This study was a secondary analysis examining the efficacy of escitalopram, problem-solving therapy (PST), or placebo administered for 1 year to prevent the onset of apathy among patients with recent stroke. Methods Patients within 3 months of an index stroke who did not meet DSM-IV diagnostic criteria for major or minor depression and who did not have a serious comorbid physical illness were enrolled. Patients were recruited from three sites: University of Iowa, University of Chicago, and Burke Rehabilitation Hospital. One hundred fifty-four patients without evidence of apathy at initial evaluation were included in the randomized controlled trial using escitalopram (10 mg patients ≤65 years; 5 mg patients >65 years) (N = 51) or placebo (N = 47) or non-blinded PST (12 total sessions) (N = 56) over 1 year. At 3, 6, 9, and 12 months, patients were assessed for diagnosis and severity of apathy using the Apathy Scale. Results Using a Cox proportional hazards model of time to onset of apathy, participants given placebo were 3.47 times more likely to develop apathy than patients given escitalopram and 1.84 times more likely to develop apathy than patients given PST after controlling for age, sex, cognitive impairment, and diabetes mellitus status (adjusted hazard ratio: 3.47, 95% CI: 1.79–6.73 [escitalopram group]; adjusted hazard ratio: 1.84, 95% CI: 1.21–2.80 [PST group]). Conclusion Escitalopram or PST was significantly more effective in preventing new onset of apathy following stroke compared with placebo.

The role of interleukin-6 (IL-6) as a risk factor for developing depressive symptoms, neuropsychological impairment, and related functional and neurological symptom severity during the acute phase of ischemic stroke is still underexplored. Here, the authors assessed this issue, in 48 patients without significant clinical history for major medical illnesses or other factors that promote inflammation, 72 hours after a first-ever acute ischemic stroke. In the acute phase of ischemic stroke, increased IL-6 plays a key role in the onset of depressive disorders, apathy/amotivation, somatic symptoms of depression, and neurological/functional symptoms, resulting in higher disability and poor outcome of stroke patients.

Although stroke is a leading cause of death in the United States and around the world, many people fear this disease because of its nonfatal neurological impairments that lead to disability or dependency. Considerable research has focused on lessening the neurological effects of the acute brain injury. To date, success is limited. Despite these research efforts, only intravenous thrombolysis and endovascular interventions are accepted as effective in limiting the acute effects of ischemic stroke. Although these therapies are efficacious, only 3% to 5% of patients with stroke are receiving reperfusion-based therapies due to the very short time windows for treatment.1 No medical or surgical intervention is useful in improving outcomes after intracerebral hemorrhage. Annually, approximately 400 000 Americans need rehabilitation to help with recovery after stroke.2 Given the magnitude of the problem, effective new therapies are needed to augment the process of recovery. These therapies could be given as adjuncts to conventional rehabilitation to these patients who have potentially disabling residual neurological impairments. Because many more patients could be treated, an effective therapy that maximizes neurological recovery might have a much bigger societal impact than emergency reperfusion therapy alone.3,4 Unfortunately, relatively few clinical studies have tested interventions that might augment recovery. The basic science understandings of the process of recovery after stroke have advanced.5–10 It is now clear that the adult brain has a real capacity for physiological and anatomic modifications that lead to motor and cognitive recovery.11 This complex process is mediated by multiple mechanisms including enhanced regional metabolism and resolution of diaschisis. Cellular changes after stroke include proliferation of neural and glial cell precursors, activation of astrocytes and inflammatory cells, migration of blood vessels, increased axonal sprouting, increased branching of dendrites, and development of new synapses.12–14 …

Objective Stroke often produces marked physical and cognitive impairments leading to functional dependence, caregiver burden, and poor quality of life. We examined the course of disability during a 1-year follow-up period after stroke among patients who were administered antidepressants for 3 months compared to patients given placebo for 3 months. Methods A total of 83 patients entered a double-blind randomized study of the efficacy of antidepressants to treat depressive disorders and reduce disability after stroke. Patients were assigned to either fluoxetine (N = 32), nortriptyline (N = 22) or placebo (N = 29). Psychiatric assessment included administration of the Present State Examination modified to identify DSM-IV symptoms of depression. The severity of depression was measured using the 17-item Hamilton Depression Rating Scale. The modified Rankin Scale was used to evaluate the disability of patients at initial evaluation and at quarterly follow-up visits for 1 year. Impairment in activities of daily living was assessed by Functional Independence Measure at the same time. Results During the 1-year follow-up period, and after adjusting for critical confounders including age, intensity of rehabilitation therapy, baseline stroke severity, and baseline Hamilton Depression Rating Scale, patients who received fluoxetine or nortriptyline had significantly greater improvement in modified Rankin Scale scores compared to patients who received placebo ( t [156] = −3.17, p=0.002). Conclusions Patients treated with antidepressants had better recovery from disability by 1-year post stroke (i.e., 9 months after antidepressants were stopped) than patients who did not receive antidepressant therapy. This effect was independent of depression suggesting that antidepressants may facilitate the neural mechanisms of recovery in patients with stroke.

Late-life depression (LLD) is a frequent complication of the ageing process, occurring in up to 5% of community-dwelling elderly and in a higher proportion of subjects with coexistent medical illnesses. Its presence has been consistently associated with cognitive impairment, greater disability and increased mortality. Approximately half of patients with LLD have evidence of subcortical ischaemic damage in prefrontal circuits revealed by MRI. This might constitute the biological substrate of the cardinal symptoms of depression and of executive dysfunction. An important proportion of patients with LLD do not achieve remission of their depressive symptoms in spite of adequate pharmacological and psychotherapeutic treatment. In addition, a group of LLD patients progress to further impairment and disability in the form of a dementing disorder. There is an imperative need to develop new treatment strategies for LLD. Non-invasive brain stimulation techniques such as repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS) are safe and efficacious interventions that might be used in combination with other therapeutic options to improve treatment outcomes. However, there are still questions regarding the optimal way in which rTMS and dTCS should be delivered as well as to the way in which we may identify the subjects who will benefit the most from these interventions.

Although major depression is one of the most frequent psychiatric disorders among patients with Parkinson's disease, diagnostic criteria have yet to be validated. The main aim of our study was to validate depressive symptoms using latent class analysis for use as diagnostic criteria for major depression in Parkinson's disease. We examined a consecutive series of 259 patients with Parkinson's disease admitted to 2 movement disorders clinics for regular follow-ups. All patients were assessed with a comprehensive psychiatric interview that included structured assessments for depression, anxiety, and apathy. The main finding was that all 9 Diagnostic and Statistical Manual (4th edition) diagnostic criteria for major depression (ie, depressed mood, diminished interest or pleasure, weight or appetite changes, sleep changes, psychomotor changes, loss of energy, feelings of worthlessness or inappropriate guilt, poor concentration, and suicidal ideation) identified a patient class (severe depression group) with high statistical significance. Latent class analysis also demonstrated a patient class with minimal depressive symptoms (no-depression group), and a third patient class with intermediate depressive symptoms (moderate depression). Anxiety and apathy were both significant comorbid conditions of moderate and severe depression. Taken together, our findings support the use of the full Diagnostic and Statistical Manual (4th edition) criteria for major depression for use in clinical practice and research in Parkinson's disease and suggest that anxiety may be included as an additional diagnostic criterion. © 2011 Movement Disorder Society

Stroke of the right MCA is common. Such strokes often have consequences for emotional experience, but these can be subtle. In such cases diagnosis is difficult because emotional awareness (limiting reporting of emotional changes) may be affected. The present study sought to clarify the mechanisms of altered emotion experience after right MCA stroke. It was predicted that after right MCA stroke the anterior cingulate cortex (ACC), a brain region concerned with emotional awareness, would show reduced neural activity. Brain activity during presentation of emotional stimuli was measured in 6 patients with stable stroke, and in 12 age- and sex-matched nonlesion comparisons using positron emission tomography and the [(15)O]H(2)O autoradiographic method. MCA stroke was associated with weaker pleasant experience and decreased activity ipsilaterally in the ACC. Other regions involved in emotional processing including thalamus, dorsal and medial prefrontal cortex showed reduced activity ipsilaterally. Dorsal and medial prefrontal cortex, association visual cortex and cerebellum showed reduced activity contralaterally. Experience from unpleasant stimuli was unaltered and was associated with decreased activity only in the left midbrain. Right MCA stroke may reduce experience of pleasant emotions by altering brain activity in limbic and paralimbic regions distant from the area of direct damage, in addition to changes due to direct tissue damage to insula and basal ganglia. The knowledge acquired in this study begins to explain the mechanisms underlying emotional changes following right MCA stroke. Recognizing these changes may improve diagnoses, management and rehabilitation of right MCA stroke victims.

The aim of this study was to investigate limbic metabolic abnormalities in remote traumatic brain injury (TBI) and their psychiatric correlates. Twenty patients and 13 age-matched comparison subjects received complete psychiatric evaluation and brain MRI and MR spectroscopy at 3 Tesla. Patients had reduced NAA to creatine ratio in the left hippocampus relative to comparison subjects (mean=1.3 [SD=0.21] compared with mean=1.55 [SD=0.21]; F=10.73, df=1, 30, p=0.003), which correlated with the Social Functioning Examination scores (r(s)=-0.502, p=0.034). Furthermore, patients with mood disorders had reduced NAA to creatine ratio in the left cingulate relative to patients without mood disorders (1.47 compared with 1.68; F=3.393, df=3, 19, p=0.044). Remote TBI displays limbic metabolic abnormalities, which correlate to social outcome and psychiatric status.

Objective: To review the world's (English-language) publications related to depression following stroke. Method: The databases from MEDLINE and PubMed were reviewed for articles related to poststroke depression (PSD), depression and cerebral vascular accident, depression and cerebral vascular disease, and depression and cerebral infarction. Results: Most studies examined prevalence rates of depression and the clinical correlates of depression. Based on pooled data, the overall prevalence of major depression was 21.7% and minor depression was 19.5%. The strongest single correlate of depression was severity of impairment in activities of daily living. However, the existence of depression at baseline was found to be associated with greater impairment at follow-up, ranging from 6 weeks to 2 years in 83% of studies. Further, depression following acute stroke was also associated with greater cognitive impairment and increased mortality. PSD has been shown in 6 double-blind controlled studies to be effectively treated with antidepressants, and 1 study has recently shown that PSD can be effectively prevented. Conclusions: During the past 20 years, significant progress has been made in the identification and treatment of depression following stroke. In the future, antidepressant treatment will likely play an increasing role in the management of patients with acute stroke. Further research is needed to identify the mechanisms of depression and why antidepressants lead to improved physical and cognitive recovery and decreased mortality.

Objective: To review the frequency, clinical correlates, and mechanism of anosognosia after stroke. Methods: We searched the most recent relevant literature on anosognosia after stroke and carried out a critical analysis of the main findings. Results: Anosognosia is present in about 10% of acute stroke patients and its diagnosis is relatively simple. Nevertheless, a valid and reliable standardization of diagnostic instruments and criteria for research purposes is more difficult to achieve. This limitation may partially account for various instruments available to assess anosognosia and the different strategies used to diagnose this phenomenon. Anosognosia is a fleeting phenomenon and chronic cases are infrequent. There is a robust association between anosognosia and right-hemisphere lesions involving cortical (insular, temporal, and parietal lobes) and subcortical structures (thalamus and basal ganglia). The main clinical correlates of anosognosia are the presence of neglect, cognitive deficits, previous strokes, and older age. Anosognosia has a negative impact on the rehabilitation of stroke patients. The mechanism of anosognosia remains unknown but was explained as owing to psychological denial, disconnexion between left and right hemispheres, and dysfunction of a system that monitors the intention to move and actual movements. Conclusion: Anosognosia is a relatively frequent complication of acute stroke and may become an excellent model to understand the mechanism of human awareness.

Objective: We will review the available evidence on the frequency, clinical correlates, mechanism, and treatment of apathy following stroke. Methods: We have explored relevant databases (that is, PubMed, MEDLINE, and PsycINFO) using the following keywords and their combinations: apathy, motivation, abulia, stroke, cerebrovascular disease, basal ganglia, prefrontal cortex, anterior cerebral infarction, and thalamus. Results: The frequency of apathy following stroke has been consistently estimated between 20% and 25%. It appears to be associated with the presence of cognitive impairment, a chronic course characterized by progressive functional decline, and with disruption of neural networks connecting the anterior cingulate gyrus, the dorsomedial frontal cortex, and the frontal pole with the ventral aspects of the caudate nucleus, the anterior and ventral globus pallidus, and the dorsomedian and intralaminar thalamic nuclei. Published treatment studies have been mostly limited to anecdotal case reports, generally using dopamine agonists or stimulant medications. Cholinesterase inhibitors and nefiracetam may significantly reduce apathetic symptoms. However, their efficacy was examined in relatively small clinical trials that require replication. Conclusion: Apathy is a frequent neuropsychiatric complication of stroke that, although often associated with depression and cognitive impairment, may occur independently of both. Its presence has been consistently associated with greater functional decline. However, there is no conclusive evidence about which is the best treatment for this condition.

Involuntary emotional expression disorder (IEED) is a syndrome characterized by involuntary episodes of emotional expression, particularly crying or laughing, that occur in patients with a neurological illness, including neuro-degenerative diseases. The authors assessed the frequency and clinical correlates of IEED among 131 patients with Parkinson's disease. IEED was present in 16.8% of patients overall and in 15.3% of depressed patients. The only clinical correlate of IEED diagnosis was greater severity of Parkinson's disease. The lack of an association between IEED and depression suggests that, in spite of some symptom overlap, the two disorders are distinct neuropsychiatric syndromes in Parkinson's disease.

Objective To determine whether family history of psychiatric disorder constitutes a risk factor for the development of poststroke depression. Design A meta-analysis setting: patients examined for depression following stroke seen in acute care, rehabilitation hospital, or outpatient care settings. Participants All patients who were reported in the world's literature in English language publications in which information was provided about the existence or not of poststroke depression and the presence or absence of a family history of psychiatric disorder. Measurements The frequency of family history of psychiatric disorder was determined for each study as well as the relationship of family history to the presence of poststroke depression. Results Based on data obtained from 903 patients with stroke, the fixed model analysis found a risk ratio of 1.51 and the random model a risk ratio of 1.46 for the existence of poststroke depression if there is a positive family history of psychiatric disorder compared with a negative family history. Conclusions The existence of a positive family history of psychiatric disorder constitutes a risk factor for development of poststroke depression. The role of family history in poststroke depression, however, appears to be substantially lower than among elderly depressed patients without evidence of vascular disease.

Psychiatric disorders, including disorders of emotion control, are common in Huntington's disease. The neurobiological mechanism of the increased rate of disorders of emotion control are not known. Emotion perception deficits have been reported in Huntington's disease, but studies of emotional experience have been limited. In the present study we aim to expand the research in emotion in Huntington's disease by examining the neural bases of induced dysphoria at an early stage of Huntington's disease. Ten Huntington's disease patients and 12 demographically matched healthy volunteers underwent [ 15 O] water positron emission tomography while in a transient state of dysphoria induced by viewing negatively charged affect-laden stimuli. Both groups experienced dysphoric mood, but Huntington's disease patients responded to the stimuli with greater arousal, anger and fear than healthy controls. Induced dysphoric mood was associated with a widespread reduction of activity within the frontal and parietal lobes, thalamus, and cerebellum. These differences could not be explained based on the smaller gray matter volumes of the corresponding regions, although in Huntington's disease patients smaller caudate nucleus volumes predicted lower dorsal-lateral prefrontal activity. Areas of increased activity included the striate and extrastriate cortex, the left thalamus, the transverse temporal gyrus, and the posterior hippocampus. This study elucidates possible mechanisms contributing to psychiatric disturbances of emotion often found in patients with Huntington's disease.

The validity, sensitivity, and specificity of depressive symptoms for the diagnosis of major depression, minor depression, dysthymic disorder, and subsyndromal depression in Parkinson's disease (PD) were examined. A consecutive series of 173 patients with PD attending a Movement Disorders Clinic underwent a comprehensive psychiatric and neurological assessment. The symptoms of loss of interest/pleasure, changes in appetite or weight, changes in sleep, low energy, worthlessness or inappropriate guilt, psychomotor retardation/agitation, concentration deficits, and suicide ideation were all significantly associated with the presence of the DSM-IV depressed mood criterion for major depression. The symptoms of changes in appetite, changes in sleep, low energy, low self-esteem, poor concentration, and hopelessness were all significantly associated with the presence of the DSM-IV criterion of sad mood for dysthymic disorder. Thirty percent of our sample met DSM-IV diagnostic criteria for major depression, 20% met diagnostic criteria for dysthymic disorder, 10% met diagnostic criteria for minor depression, and 8% met clinical criteria for subsyndromal depression. Patients with either major or minor depression had significantly more severe deficits in activities of daily living, more severe cognitive impairments, and more severe Parkinsonism than patients with either dysthymic disorder or no depression. This study provides validation to the DSM-IV diagnostic criteria for major depression and dysthymic disorder for use in PD. The categories of minor and subsyndromal depression may need further validation.

The authors randomly assigned nondepressed patients at least 3 months poststroke to receive nortriptyline, fluoxetine, or placebo for 3 months using double-blind methodology. Patients were followed at 3, 6, 9, and 21 months for new onset of depression. In patients treated with antidepressants, lesion volume and degree of social impairment were associated with subsequent late-onset of poststroke depression at 6 and 9 months. In the placebo group, severity of impairment in activities of daily living, at 3 and 9 months, was associated with late onset poststroke depression. Differences in the clinical/pathological correlates may reflect subtle differences in the pathophysiology of poststroke depression following prophylactic antidepressants.

Anosognosia is the lack of awareness or the underestimation of a specific deficit in sensory, perceptual, motor, affective or cognitive functioning due to a brain lesion. This self-awareness deficit has been studied mainly in stroke hemiplegic patients, who may report no deficit, overestimate their abilities or deny that they are unable to move a paretic limb. In this review, a detailed search of the literature was conducted to illustrate clinical manifestations, pathogenetic models, diagnostic procedures and unresolved issues in anosognosia for motor impairment after stroke. English and French language papers spanning the period January 1990-January 2007 were selected using PubMed Services and utilizing research words stroke, anosognosia, awareness, denial, unawareness, hemiplegia. Papers reporting sign-based definitions, neurological and neuropsychological data and the results of clinical trials or historical trends in diagnosis were chosen. As a result, a very complex and multifaceted phenomenon emerges, whose variable behavioural manifestations often produce uncertainties in conceptual definitions and diagnostic procedures. Although a number of questionnaires and diagnostic methods have been developed to assess anosognosia following stroke in the last 30 years, they are often limited by insufficient discriminative power or a narrow focus on specific deficits. As a consequence, epidemiological estimates are variable and incidence rates have ranged from 7 to 77% in stroke. In addition, the pathogenesis of anosognosia is widely debated. The most recent neuropsychological models have suggested a defect in the feedforward system, while neuro-anatomical studies have consistently reported on the involvement of the right cerebral hemisphere, particularly the prefrontal and parieto-temporal cortex, as well as insula and thalamus. We highlight the need for a multidimensional assessment procedure and suggest some potentially productive directions for future research about unawareness of illness.

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.

While the role of the cerebellum in motor coordination is widely accepted, the notion that it is involved in emotion has only recently gained popularity. To date, functional neuroimaging has not been used in combination with lesion studies to elucidate the role of the cerebellum in the processing of emotional material. We examined six participants with cerebellar stroke and nine age and education matched healthy volunteers. In addition to a complete neuropsychological, neurologic, and psychiatric examination, participants underwent [15O]water positron emission tomography (PET) while responding to emotion-evoking visual stimuli. Cerebellar lesions were associated with reduced pleasant experience in response to happiness-evoking stimuli. Stroke patients reported an unpleasant experience to frightening stimuli similar to healthy controls, yet showed significantly lower activity in the right ventral lateral and left dorsolateral prefrontal cortex, amygdala, thalamus, and retrosplenial cingulate gyrus. Frightening stimuli led to increased activity in the ventral medial prefrontal, anterior cingulate, pulvinar, and insular cortex. This suggests that alternate neural circuitry became responsible for maintaining the evolutionarily critical fear response after cerebellar damage.

Objective— We previously reported preliminary data (N=14) demonstrating a significant and positive relationship between forearm vascular function and neuropsychological performance in individuals with atherosclerotic vascular disease (AVD). The current study was conducted to confirm and extend those findings in a much larger, nonoverlapping sample. Methods and Results— Participants were 82 individuals with AVD, with no history of stroke, cardiac surgery, or dementia. Forearm vascular function was measured before and after brachial artery infusion of vasoactive agents (acetylcholine, nitroprusside, verapamil). Neuropsychological functioning was assessed with the Repeatable Battery for the Assessment of Neuropsychological Status. Statistical analysis included multiple regression and partial correlations, controlling for education. Vascular function was significantly and positively associated with neuropsychological performance [R 2 change=0.116, F change (3,74)=3.72, P =0.015]. Follow-up analyses indicated that smooth muscle function was the aspect of vascular function most strongly associated with neuropsychological performance. Individual vascular risk factors were not significantly associated with neuropsychological performance when controlling for vascular function. Conclusions— Better vascular function is significantly associated with better neuropsychological performance in individuals with AVD. It is possible that this relationship exists in healthy elderly individuals as well, although this cannot be determined based on the existing data, because a healthy comparison group was not studied. With additional research, measures of vascular function might be useful in the early identification of individuals who are at greatest risk for developing vascular cognitive impairment.

Proton MR spectroscopy (1HMRS) has been extensively used among mood disorders patients. A review of the published literature in 1HMRS studies of mood disorders was carried out for the period 1991 to July 2006. Of 71 1HMRS studies, 77.5% were done at 1.5T and 66.2% used single voxel sequences (SVS), implying limitations of spectral resolution and anatomic coverage, respectively. In all, 47.9% of studies relied on creatine (Cr) as internal signal standard, although Cr changes were reported in major depression (MD). Most reported metabolic alterations related to mood state affected the left frontal lobe. Depressed adult and pediatric MD patients had reduced glutamate (Glu) in frontal lobe regions, which reversed with successful treatment. A consistent reduction of N-acetyl-aspartate (NAA) was reported in the hippocampal formation among bipolar disorder (BD) patients, along with an increment in frontal Glu. The differences in results of 1HMRS studies in mood disorders reflect heterogeneity of technical factors and subject selection. Future studies should benefit from higher spectral resolution and more extensive anatomic coverage as well as standardized data-processing protocols and subject selection criteria. J. Magn. Reson. Imaging 2007. © 2007 Wiley-Liss, Inc.

Characteristics associated with life expectancy in Alzheimer's disease (AD) are still far from known. Here we aimed at examining the ability of baseline/longitudinal clinical variables to predict time to death. One-hundred fifty AD outpatients underwent diagnostic, neuropsychiatric, and functional assessment at baseline (when ApoE ɛ4 was also investigated) and at each subsequent annual visit. A random effects joint modeling approach was used to simultaneously model the baseline and longitudinal trajectory of each factor and predict the time to death, adjusting for demographic covariates. An ancillary analysis of ApoE ɛ4 status as a predictor was also conducted. Kaplan-Meier survival curves were constructed to elucidate the relationship between each factor and the estimated probability of death over time. Shorter survival was associated with male gender, higher education, older age, lower cognition, and worse functioning in daily life, but not ApoE ɛ4 status. Longitudinal trajectories increased predictive power over using just baseline levels highlighting apathy, and secondarily aberrant motor behaviors and sleep disorders, as a highly reliable predictor for mortality. Apathy was the strongest neuropsychiatric predictor of time to death, which supports its role in the pathogenesis of the disorder. An increased knowledge of factors modulating survival in AD is a strategic prerequisite to plan therapeutic interventions.

Objectives The objectives of this study were to determine whether anosognosia, depression, and elevated mood are associated with delusions in Alzheimer disease (AD), and to examine the validity of standardized diagnostic criteria for psychosis of dementia. Method The authors assessed a consecutive series of 771 patients with AD attending a dementia clinic with a comprehensive neuropsychologic and psychiatric evaluation that included specific measures of delusions, hallucinations, anosognosia, depression, and elevated mood. Results Delusions were found in one-third of the patients and hallucinations in 7%. Most patients with hallucinations also had delusions. A principal component analysis of the Psychosis Dementia Scale, which rates the presence and severity of delusions, produced the factors of paranoid misidentification and expansive delusions. Paranoid, but not expansive, delusions increased across the stages of the illness. Anosognosia and depression were significantly and independently associated with the presence of delusions, whereas elevated mood was significantly associated with expansive, but not paranoid, delusions. A multiple logistic regression analysis demonstrated that delusions in AD were significantly associated with depression, anosognosia, overt aggression, and agitation. Conclusions Anosognosia, depression, global cognitive deficits, and elevated mood are the main psychiatric correlates of paranoid misidentification and expansive delusions in AD, whereas overt aggression and agitation are the most frequent behavioral concomitants of psychosis in AD.

Chan K-L, Campayo A, Moser DJ, Arndt S, Robinson RG. Aggressive behavior in patients with stroke: association with psychopathology and results of antidepressant treatment on aggression. Objective To examine, in a post hoc analysis of an antidepressant treatment trial, correlates of irritability and aggression after stroke and changes in irritability scores associated with antidepressant treatment. Design Aggressive patients (n=23) were compared with nonaggressive patients (n=69) on numerous measures of psychopathology, poststroke impairment, and neuroimaging findings. Setting All patients were hospitalized at the time of the initial evaluation for acute stroke or for rehabilitation therapy. Participants Ninety-two patients from the Iowa City Stroke Study were classified as aggressive or nonaggressive, based on symptoms elicited by the Present State Examination (PSE) and from family or caretaker reports. Intervention All patients were randomized to receive nortriptyline, fluoxetine, or placebo using a double-blind methodology. Main Outcome Measure The change in aggression score as elicited by the PSE at the beginning and the end of a 12-week treatment trial. Results Twenty-five percent (23/92) of patients reported irritability or aggression. Irritable and aggressive patients had higher total PSE scores, Hamilton Depression Rating Scale scores, Hamilton Anxiety Rating Scale (HAMA) scores, and lower Mini-Mental State Examination scores. They also had lesions that were more proximal to the frontal pole. Stepwise regression analysis showed that HAMA scores and proximity of lesion to the frontal pole were significant independent predictors of irritability. Among irritable and aggressive patients with depression who responded to antidepressants, there was a significantly greater reduction in irritability after treatment, compared with patients whose depression did not lessen with treatment. Conclusions Several factors, such as severity of impairment, other psychopathology, and neurobiologic factors, appear to contribute to irritable and aggressive behavior in stroke patients. If depression accompanies aggression, the results of this small study suggest that successful treatment of depression may reduce aggressive behavior.

The authors examined the prevalence and clinical correlates of pathological laughing and crying (PLC) using the Pathological Laughter and Crying Scale (PLAC) in 92 consecutive patients with acute symptoms 3, 6, and 12 months after traumatic brain injury (TBI). The prevalence of PLC during the first year after TBI was 10.9%. Compared to patients without PLC, patients with PLC had significantly more depressive, anxious, and aggressive behaviors and had poorer social functioning. Additionally, PLC was associated with the presence of anxiety disorder, and focal frontal lobe lesions, especially in the lateral aspect of the left frontal lobe. Findings revealed that prefrontal regulation of limbic circuits may be involved in the pathophysiology of this disturbed emotional expression.

The First Conference on Menthol Cigarettes wasconvened in Atlanta, Georgia, on March 21–22, 2002.The purpose of the conference was to evaluate thepresent state of the science concerning the potentialincreased harm caused by adding menthol to cigar-ettes, and to set the priorities for further studies ofmenthol cigarettes. More than 80 researchers andtobacco control experts participated in the conference.This supplement to Nicotine & Tobacco Researchprovides a summary of the state of our knowledge ofthe history, sociology, epidemiology, and toxicologyof menthol cigarettes as well as the proposed futureresearch agenda.IntroductionMenthol is unique in that it is the only cigaretteadditive actively marketed to consumers. It is the onlyaspect of cigarette design that is marketed explicitlybased on its physiological effects, as an anti-irritantand a cooling agent. It is the only cigarette additiveabout which consumers make conscious buyingchoices.Although the tobacco industry has activelyinvestigated menthol as an additive (Best, 1993;Borgerding, 1993; Borschke, 1993; Hopp, 1993;Reid, 1993; Wilson, 1993), relatively few studieshave been published in the public health literatureabout the following topics

Background Depression has a significant impact on poststroke recovery and mortality. There are a proportion of patients with poststroke depression (PSD) who do not respond to antidepressants. Repetitive Transcranial Magnetic Stimulation (rTMS) might be a safe and effective alternative in these refractory cases. Methods We conducted a randomized, parallel, double-blind study of active versus sham left prefrontal rTMS in patients with refractory PSD. After discontinuing antidepressants, patients were randomly assigned to receive 10 sessions of active (10 Hz, 110% of the motor threshold, 20 trains of 5 seconds duration) or sham left prefontal rTMS. Efficacy measures included HAM-D scores, response and remission rates. Patients completed a neuropsychological battery at baseline and after completing the protocol. Results When compared with sham stimulation, 10 sessions of active rTMS of the left dorsolateral prefrontal cortex were associated with a significant reduction of depressive symptoms. This reduction was not influenced by patient’s age, type or location of stroke, volume of left frontal leukoaraiosis or by the distance of the stimulating coil to the prefrontal cortex. However, there was a significant positive correlation between the percentage of reduction of Ham-D scores and frontal gray and white matter volumes. There were no significant changes in cognitive functioning between the active and the sham stimulation groups. In addition, there were few and mild adverse effects that were equally distributed among groups. Conclusions Taken together, these preliminary findings suggest that rTMS may be an effective and safe treatment alternative for patients with refractory depression and stroke.

In recent years, poststroke depression has attracted worldwide interest. This review focuses on the major research themes that have emerged. Pooled data from studies conducted throughout the world have found prevalence rates for major depression of 19.3% among hospitalized patients and 23.3% among outpatient samples. The diagnosis of poststroke depression is most appropriately based on a structured mental state exam and DSM-IV criteria for depression due to stroke with major depressive-like episode or depressive features. Rarely, poststroke patients may also develop bipolar mood disorder. The treatment of poststroke depression has been examined in several placebo-controlled randomized clinical trials with both nortriptyline and citalopram showing efficacy. The progression of recovery following stroke can be altered by treating depression, which has been shown to improve recovery in activities of daily living and cognitive impairment and to decrease mortality. In addition, two studies have demonstrated that poststroke depression can be prevented using antidepressant medication, which also decreases the frequency of associated physical illness. Furthermore, two studies have shown that premorbid depression can significantly increase the risk of stroke over the subsequent 10-15 years. The mechanisms underlying the association of cerebrovascular diseases and mood disorder are important areas for future investigation.

Cognitive impairment is common after stroke and may be caused by poststroke depression. Remission of poststroke major depression after treatment has been associated with improvement in cognitive function. The current study was designed to examine how long that cognitive improvement lasts and to compare depressed patients' cognitive status with that of nondepressed patients with comparable lesions.Seventeen patients with poststroke depression and cognitive impairment who had early and sustained remission of their depression during a double-blind treatment study were compared with 42 nondepressed stroke patients who remained nondepressed throughout the follow-up. Mood and cognitive function were followed-up over 2 years with the Hamilton Depression Rating Scale and Mini-Mental State Examination (MMSE).In the patients with early and sustained remission of depression, there was rapid improvement of cognitive function, which was maintained over 2 years. Their initial MMSE score of 23.3 (SD=4.2) improved to 26.6 (SD=3.5) at 3 months and was 26.1 (SD=3.6) at 2 years. The nondepressed patients showed essentially no change in cognitive function over 2 years (initial MMSE score: mean=26.3, SD=3.1; score at 2-year follow-up: mean=25.7, SD=4.1).Cognitive function, once improved after remission of poststroke depression, is likely to remain stable over the next 2 years in the absence of subsequent reinjury to the central nervous system. Cognitive impairment due to poststroke depression is reversible and can be quantified separately from cognitive impairment on the basis of the location and extent of ischemic brain damage.

Objective The existence of anxiety disorders plays an important role in the prognosis and associated impairment among patients with poststroke depression. The authors examined the efficacy of nortriptyline treatment for patients with comorbid generalized anxiety disorder (GAD) and depression after stroke. Methods Data from three studies were merged to provide 27 patients with comorbid GAD and depression, who participated in double-blind treatment studies comparing nortriptyline (N=13) and placebo (N=14). Severity of anxiety was measured with the Hamilton Rating Scale for Anxiety (Ham-A), and severity of depression was measured with the Hamilton Rating Scale for Depression (Ham-D). Activities of daily living were assessed by use of the Johns Hopkins Functioning Inventory (JHFI). Results There were no significant differences between the nortriptyline and placebo groups in demographic characteristics, stroke type, and neurological findings. Patients receiving nortriptyline treatment showed significantly greater improvement on the Ham-A, Ham-D, and JHFI than patients receiving placebo. The anxiety symptoms showed earlier improvement than depressive symptoms in patients treated with nortriptyline. Conclusions These findings suggest that poststroke GAD comorbid with poststroke depression may be effectively treated with nortriptyline, and data indicate the need for a trial specifically designed to examine treatment of anxiety disorder.

The authors assessed aggressive behavior in 89 patients with traumatic brain injury (TBI) and 26 patients with multiple trauma but without TBI using a quantitative scale (the Overt Aggression Scale) and examined its clinical correlates. Aggressive behavior was found in 33.7% of TBI patients and 11.5% of patients without TBI during the first 6 months after injury. Aggressive behavior was significantly associated with the presence of major depression, frontal lobe lesions, poor premorbid social functioning, and a history of alcohol and substance abuse. Interventions aimed at treatment of depression and substance abuse and enhancing social support may help reduce the severity of this disruptive behavior.

OBJECTIVE Authors compared poststroke major (n = 17) or minor (n = 28) depression diagnosed 3 to 6 months poststroke with major (n = 16) or minor (n = 22) depression diagnosed at 12 to 24 months to identify changes in the phenomenological characteristics of poststroke depression over time. METHODS Depressive symptoms were divided into vegetative, psychological symptoms, and melancholic features elicited by the Present State Exam (PSE). Patients were also examined for severity of depression, social impairment, and neurological findings. RESULTS Early-onset poststroke major depression was associated with a higher frequency of vegetative symptoms and larger lesion volume than late-onset major depression. Similarly, early-onset minor depression was associated with poorer social functioning and a higher frequency of melancholic, vegetative, and psychological symptoms than late-onset minor depression. CONCLUSION These findings suggest that the phenomenological characteristics of both major and minor poststroke depression change over time and that both early-onset major and minor poststroke depression may result from similar etiological mechanisms provoked by brain injury.

Background: Stroke is a major health problem and poststroke depression is known to be one of the frequent and severe psychiatric complications following stroke. Methods: Based on the results of structured psychiatric mental state exams and DSM diagnostic criteria, the prevalence of poststroke depression has been examined in numerous study populations throughout the world. Longitudinal examinations have documented the effect of poststroke depression on recovery from stroke. Results: The mean prevalence of poststroke major depression was 21.1 % and minor depression was 17.1% among hospitalized or outpatient samples. Community samples showed a slightly lower rate of 14.1% and 9.1%, respectively. Furthermore, the existence of poststroke depression leads to poorer physical recovery, greater cognitive impairment, and worse recovery in activities of daily living compared with non-depressed patients. Several studies have also found that poststroke depression is associated with increased mortality compared with non-depressed patients who had comparable strokes and similar premorbid risk factors. Finally, several studies have found that successful treatment of poststroke depression improves both cognitive and physical recovery and decreases mortality. Conclusion: The current review documents the beneficial effect of identifying and treating poststroke depression on both recovery and survival following stroke.

This study examined the effect of antidepressants in preventing depression after stroke. Nondepressed poststroke patients (N = 48) were randomly assigned to receive nortriptyline, fluoxetine, or placebo for 3 months by using double-blind methodology and were followed-up for 21 months by using a naturalistic design. During the treatment period, one minor depression developed in the nortriptyline group (n = 13 at 3 months), one minor depression developed in the fluoxetine group (n = 13), and five minor depressions developed in the placebo group (n = 15; p

Neuropsychiatric and cognitive symptoms are common in patients with Parkinson's disease (PD) from the early stage of the disease but their course is still unclear. In this study we investigated prospectively the progression of affective and cognitive symptoms and disorders in de novo idiopathic PD patients. Twenty-four de novo drug naïve PD patients underwent a comprehensive neurological, psychopathological and neuropsychological evaluation at the first diagnostic visit (OFF), after 4-6 months when the antiparkinsonian therapy regimen was stabilized (ON-1), and at one year following the ON-1 follow-up visit (ON-2). Generalized least squares analysis revealed a significant improvement over time in the depressive mood, short and long term episodic verbal memory, visual memory, and the motor symptoms. Pairwise comparisons showed a significant change from OFF to ON-1 for all the aforementioned variables, except for short term episodic verbal memory which approached significance. A significant improvement from ON-1 to ON-2, however, was shown for short term episodic verbal memory. An ancillary analysis indicated that overall level and change in a number of cognitive variables, but not depression, was conditional upon age of onset, education, and sometime gender. In conclusion, early stage PD is not associated with affective and cognitive deterioration. On the contrary, very specific neuropsychiatric and cognitive symptoms may improve. This study provides Class III evidence that antiparkinsonian treatment commonly used in the clinical practice improves memory performance and depression severity in de novo patients with PD.

INTRODUCTION Previous research suggests that African American smokers may have improved outcomes if interventions are culturally specific. However, few interventions sufficiently address the unique needs of this population in a format with large reach potential. The purpose of this study was to test the efficacy of a newly developed digital video disc (DVD)-based cessation intervention targeting African Americans. METHODS In a 2-arm randomized trial, smokers (N = 140) were randomly assigned to view either the new Pathways to Freedom (PTF) DVD or a standard control DVD. Participants were assessed at baseline, immediately postviewing the DVD, and at a 1-month follow-up. The primary outcomes were feasibility and process variables, including intervention evaluations, readiness to quit, and risk perceptions, and smoking-related behavior changes were examined as secondary outcomes. RESULTS Findings demonstrated the hypothesized positive effects of the PTF DVD compared with the control DVD on content evaluations, risk perceptions, and readiness to quit at follow-up. CONCLUSIONS We found initial evidence for the efficacy of the PTF DVD as a stand-alone intervention. Future research will test the efficacy of the DVD for smoking cessation in a larger randomized trial. The ultimate goal of this research is to validate a new intervention for an underserved community of smokers that can be used in multiple settings, such as community health clinics, primary care, quitlines, cessation clinics, and seminars/workshops.

This study examined the efficacy of antidepressant treatment for preventing the onset of generalized anxiety disorder (GAD) among patients with recent stroke. Of 799 patients assessed, 176 were randomized, and 149 patients without evidence of GAD at the initial visit were included in this double-blind treatment with escitalopram (N=47) or placebo (N=49) or non-blinded problem-solving therapy (PST; 12 total sessions; N=53). Participants given placebo over 12 months were 4.95 times more likely to develop GAD than patients given escitalopram and 4.00 times more likely to develop GAD than patients given PST. Although these results should be considered preliminary, the authors found that both escitalopram and PST were effective in preventing new onset of post-stroke GAD.

A total of 496 patients were examined for suicidal ideation during the acute hospital period and at 3, 6, 12, and 24 months' follow-up after suffering either stroke, traumatic brain injury, myocardial infarction, or spinal cord injury. A total of 7.3% of patients had suicidal ideation during the in-hospital evaluation (acute-onset suicidal ideation), and 11.3% developed it during the chronic 3 to 24 month rehabilitation period (delayed-onset suicidal ideation). Compared with delayed-onset suicidal patients, acute-onset suicidal patients had more predisposing risk factors (i.e., personal psychiatric history and alcohol abuse/dependence) and less social support (i.e., lower frequency of being married). Both acute and delayed-onset suicidal ideation, however, were strongly associated with the existence of major depression and impaired social functioning. These findings suggest that the detection and appropriate treatment of depressive disorders and social isolation may be the most important factor in preventing suicide both during the acute and chronic period following life-threatening physical illnesses.