Sidney Zisook

Is it possible to be schizophrenic yet neuropsychologically normal

This study identified and characterized a group of schizophrenic patients without neuropsychological (NP) impairment. A comprehensive NP battery was administered to 171 schizophrenic outpatients and 63 normal comparison participants. Each participants NP status was classified through blind clinical ratings by 2 experienced neuropsychologists; 27% of the schizophrenics were classified as NP normal. The NP-normal and NP-impaired schizophrenics were similar in terms of most demographic, psychiatric, and functional characteristics, except that NP-normal patients had less negative and extrapyramidal symptoms, were on less anticholinergic medication, socialized more frequently, and were less likely to have had a recent psychiatric hospitalization. The existence of NP-normal schizophrenics suggests that the pathophysiology underlying the cognitive deficits often associated with schizophrenia may be distinct from that causing some of its core psychiatric features.

Difference in Treatment Outcome in Outpatients With Anxious Versus Nonanxious Depression: A STAR*D Report

OBJECTIVE About half of outpatients with major depressive disorder also have clinically meaningful levels of anxiety. The authors conducted a secondary data analysis to compare antidepressant treatment outcomes for patients with anxious and nonanxious major depression in Levels 1 and 2 of the STAR*D study. METHOD A total of 2,876 adult outpatients with major depressive disorder, enrolled from 18 primary and 23 psychiatric care sites, received citalopram in Level 1 of STAR*D. In Level 2, a total of 1,292 patients who did not remit with or tolerate citalopram were randomly assigned either to switch to sustained-release bupropion (N=239), sertraline (N=238), or extended-release venlafaxine (N=250) or to continue taking citalopram and receive augmentation with sustained-release bupropion (N=279) or buspirone (N=286). Treatment could last up to 14 weeks in each level. Patients were designated as having anxious depression if their anxiety/somatization factor score from the 17-item Hamilton Depression Rating Scale (HAM-D) was 7 or higher at baseline. Rates of remission and response as well as times to remission and response were compared between patients with anxious depression and those with nonanxious depression. RESULTS In Level 1 of STAR*D, 53.2% of patients had anxious depression. Remission was significantly less likely and took longer to occur in these patients than in those with nonanxious depression. Ratings of side effect frequency, intensity, and burden, as well as the number of serious adverse events, were significantly greater in the anxious depression group. Similarly, in Level 2, patients with anxious depression fared significantly worse in both the switching and augmentation options. CONCLUSIONS Anxious depression is associated with poorer acute outcomes than nonanxious depression following antidepressant treatment.

Complicated grief and related bereavement issues for DSM‐5

Bereavement is a severe stressor that typically incites painful and debilitating symptoms of acute grief that commonly progresses to restoration of a satisfactory, if changed, life. Normally, grief does not need clinical intervention. However, sometimes acute grief can gain a foothold and become a chronic debilitating condition called complicated grief. Moreover, the stress caused by bereavement, like other stressors, can increase the likelihood of onset or worsening of other physical or mental disorders. Hence, some bereaved people need to be diagnosed and treated. A clinician evaluating a bereaved person is at risk for both over‐and under‐diagnosis, either pathologizing a normal condition or neglecting to treat an impairing disorder. The authors of DSM IV focused primarily on the problem of over‐diagnosis, and omitted complicated grief because of insufficient evidence. We revisit bereavement considerations in light of new research findings. This article focuses primarily on a discussion of possible inclusion of a new diagnosis and dimensional assessment of complicated grief. We also discuss modifications in the bereavement V code and refinement of bereavement exclusions in major depression and other disorders. Depression and Anxiety, 2011.

Psychiatric Disorders in Patients With Fibromyalgia: A Multicenter Investigation

The authors conducted an investigation in four tertiary-care centers to determine if psychiatric comorbidity and psychological variables were predictive of functional impairment in patients with fibromyalgia syndrome (FMS). Seventy-three individuals were administered the Structured Clinical Interview for DSM-III-R, the Rand 36-item Health Survey (SF-36), and multiple self-report measures. The patients with FMS were found to have a high lifetime and current prevalence of major depression and panic disorder. The most common disorders were major depression (lifetime [L] = 68%, current [C] = 22%); dysthymia (10% [C only]); panic disorder (L = 16%, C = 7%); and simple phobia (L = 16%, C = 12%). The self-report scales revealed significant elevations in depression, anxiety, neuroticism, and hypochondriasis. Functional impairment on all measures of the SF-36 was severe (e.g., physical functioning = 45.5 and role limitations due to physical problems = 20.0). Stepwise multiple-regression analysis revealed that current anxiety was the only variable that predicted a significant proportion of the variance (29%) in SF-36 physical functioning. Thus, in this multicenter study, the persons with FMS exhibited marked functional impairment, high levels of some lifetime and current psychiatric disorders, and significant current psychological distress. Current anxiety level appears to be an important correlate of functional impairment in individuals with FMS.

Handbook of bereavement: The course of normal grief

Writing an essay on the course of normal grief is more difficult than immediately meets the eye. Grief is a natural phenomenon that occurs after the loss of a loved one. If grief is normal, what, then, is “normal” grief? In our experience, grief is such an individualized process - one that varies from person to person and moment to moment and encompasses simultaneously so many facets of the bereaveds being - that attempts to limit its scope or demarcate its boundaries by arbitrarily defining normal grief are bound to fail. With this in mind, the rest of this chapter should be read not so much as prescriptive of how the normal course of grief should run but, rather, descriptive of the many and varied ways people grieve the death of a significant other. We begin with a brief review of the stages of grief, its expected duration, and definitions and purported determinants of griefs resolution. Following a discussion of the limitations of the approach, we outline a multidimensional approach to understanding the phenomena and course of grief and supplement the discussion with data from our own work on the multidimensional assessment of widowhood. The stages of grief In a similar manner to Kubler-Rosss conceptualization of staging death and dying (1969), many investigators of the process of grief and bereavement have proposed stages of normal grief (Bowlby, 1980/1981; Glick, Weiss, & Parkes, 1974; Pollock, 1987).

The nature of learning and memory impairments in schizophrenia.

The California Verbal Learning Test was used to characterize the learning and memory impairment in schizophrenia (SC) and to evaluate potential clinical and demographic factors associated with this impairment. SC patients (n = 175) performed worse than normal comparison (NC) subjects (n = 229) on all learning, recall, and recognition memory measures. The most important clinical correlates of these impairments were earlier age of onset, more negative symptoms, and greater anticholinergic medication dosage. SC patients showed a prominent retrieval deficit as indicated by disproportionate improvement when tested in a recognition, rather than a free recall, format. A residual impairment seen with recognition testing suggests a mild encoding deficit as well. In contrast, the relative absence of a storage deficit is suggested by the lack of rapid forgetting. Using a discriminant function analysis that differentiates cortical dementia [i.e., Alzheimers disease (AD)], subcortical dementia [i.e., Huntingtons disease (HD)], and normals, it was found that 50% of the SC patients were classified as having a subcortical memory profile and 35% were classified as having a normal profile, whereas only 15% were classified as having a cortical memory profile. Although these findings reflect the clinical heterogeneity often found in SC, results suggest that most SC patients demonstrate a pattern of learning and memory impairments that resembles the pattern seen in patients with primary subcortical (specifically striatal) pathology.

Suicide risk in schizophrenia: learning from the past to change the future

Suicide is a major cause of death among patients with schizophrenia. Research indicates that at least 5–13% of schizophrenic patients die by suicide, and it is likely that the higher end of range is the most accurate estimate. There is almost total agreement that the schizophrenic patient who is more likely to commit suicide is young, male, white and never married, with good premorbid function, post-psychotic depression and a history of substance abuse and suicide attempts. Hopelessness, social isolation, hospitalization, deteriorating health after a high level of premorbid functioning, recent loss or rejection, limited external support, and family stress or instability are risk factors for suicide in patients with schizophrenia. Suicidal schizophrenics usually fear further mental deterioration, and they experience either excessive treatment dependence or loss of faith in treatment. Awareness of illness has been reported as a major issue among suicidal schizophrenic patients, yet some researchers argue that insight into the illness does not increase suicide risk. Protective factors play also an important role in assessing suicide risk and should also be carefully evaluated. The neurobiological perspective offers a new approach for understanding self-destructive behavior among patients with schizophrenia and may improve the accuracy of screening schizophrenics for suicide. Although, there is general consensus on the risk factors, accurate knowledge as well as early recognition of patients at risk is still lacking in everyday clinical practice. Better knowledge may help clinicians and caretakers to implement preventive measures.This review paper is the results of a joint effort between researchers in the field of suicide in schizophrenia. Each expert provided a brief essay on one specific aspect of the problem. This is the first attempt to present a consensus report as well as the development of a set of guidelines for reducing suicide risk among schizophenia patients.

Saccadic system functioning among schizophrenia patients and their first-degree biological relatives

In Study 1, 30 schizophrenia Ss and 27 nonpsychiatric comparison Ss were presented with a fixation task, a visually guided reflexive saccade (prosaccade) task, a predictive tracking task (0.4-Hz square wave), and an antisaccade task. The 2 groups did not differ on either the fixation or prosaccade tasks. Schizophrenia Ss had an increased number of errors on the antisaccade task and had decreased rightward visually guided saccade amplitudes during the predictive tracking task. In Study 2, 13 psychiatric comparison Ss and 32 first-degree biological relatives of the schizophrenia Ss were compared with the schizophrenia Ss and a larger and older sample of nonpsychiatric Ss (n = 33) on the predictive tracking and antisaccade tasks. The groups did not differ on predictive saccadic tracking. The schizophrenia Ss and their first-degree biological relatives made more errors on the antisaccade task than both the nonpsychiatric and psychiatric comparison groups (who did not significantly differ). Results are consistent with the notion that dysfunction of dorsolateral prefrontal cortex, caudate nucleus, or both is related to liability for schizophrenia.

A placebo-controlled randomized clinical trial of nortriptyline for chronic low back pain

&NA; To assess the efficacy of nortriptyline, a tricyclic antidepressant, as an analgesic in chronic back pain without depression, we conducted a randomized, double‐blind, placebo‐controlled, 8‐week trial in 78 men recruited from primary care and general orthopedic settings, who had chronic low back pain (pain at T‐6 or below on a daily basis for 6 months or longer). Of these 57 completed the trial; of the 21 who did not complete, four were withdrawn because of adverse effects. The intervention consisted of inert placebo or nortriptyline titrated to within the therapeutic range for treating major depression (50–150 ng/ml). The main outcome endpoints were pain (Descriptor Differential Scale), disability (Sickness Impact Profile), health‐related quality of life (Quality of Well‐Being Scale), mood (Beck Depression Inventory, Spielberger State Anxiety Inventory, Hamilton Anxiety/Depression Rating Scales), and physician rated outcome (Clinical Global Impression). Reduction in pain intensity scores was significantly greater for participants randomized to nortriptyline (difference in mean change 1.68, 95% −0.001, CI −3.36, P=0.050), with a reduction of pain by 22% compared to 9% on placebo. Reduction in disability marginally favored nortriptyline (P=0.055), but health‐related quality of life, mood, and physician ratings of overall outcome did not differ significantly between treatments. Subgroup analyses of study completers supported the intent‐to‐treat analysis. Also, completers with radicular pain on nortriptyline (n=5) had significantly (P<0.05) better analgesia and overall outcome than did those on placebo (n=6). The results suggest noradrenergic mechanisms are relevant to analgesia in back pain. This modest reduction in pain intensity suggests that physicians should carefully weigh the risks and benefits of nortriptyline in chronic back pain without depression.

PTSD Following Bereavement

Until quite recently, the only stressor considered consistent with the diagnosis of PTSD was a catastrophic, out of the ordinary, trauma that almost anyone could be expected to have a severe reaction to. Thus, PTSD was considered relatively rare among non-military populations. More recently, epidemiologic surveys have suggested that PTSD may be much more prevalent than heretofore recognized, and the DSM-IV has opened the door to a much larger variety of stressors (the “A” criterion). Yet, bereavement is not considered the type of stressor capable of producing PTSD. In this study, 350 newly bereaved widows and widowers were assessed for the prevalence of PTSD, its chronicity, comorbidity, and consequences. The diagnosis of PTSD was made on the basis of questionnaire items approximating the DSM-IV criteria for PTSD. At 2 months after the spouses death, 10% of those whose spouses died after a chronic illness met criteria for PTSD, 9% of those whose spouses died unexpectedly met criteria, and 36% of those whose spouses died from “unnatural” causes (suicide or accident) had PTSD. Symptoms tended to be chronic in at least 40% of the subjects, almost always were associated with comorbid depression, and created substantial morbidity. The results suggested that PTSD may occur after bereavement, and, by extension, other stressors not recognized by official diagnostic systems. The “A” criterion needs further examination.