Anhedonia in adolescents at transdiagnostic familial risk for severe mental illness: Clustering by symptoms and mechanisms of association with behavior.

BACKGROUND: Anhedonia is a transdiagnostic symptom of severe mental illness (SMI) and emerges during adolescence. Possible subphenotypes and neural mechanisms of anhedonia in adolescents at risk for SMI are understudied. METHODS: Adolescents at familial risk for SMI (N = 81) completed anhedonia (e.g., consummatory, anticipatory, social), demographic, and clinical measures and one year prior, a subsample (N = 46) completed fMRI scanning during a monetary reward task. Profiles were identified using k-means clustering of anhedonia type and differences in demographics, suicidal ideation, impulsivity, and emotional processes were examined. Moderation analyses were conducted to investigate whether levels of brain activation of reward regions moderated the relationships between anhedonia type and behaviors. RESULTS: Two-clusters emerged: a high anhedonia profile (high-anhedonia), characterized by high levels of all types of anhedonia, (N = 32) and a low anhedonia profile (low-anhedonia), characterized by low levels of anhedonia types (N = 49). Adolescents in the high-anhedonia profile reported more suicidal ideation and negative affect, and less positive affect and desire for emotional closeness than low-anhedonia profile. Furthermore, more suicidal ideation, less positive affect, and less desire for emotional closeness differentiated the familial high-risk, high-anhedonia profile adolescents from the familial high-risk, low-anhedonia profile adolescents. Across anhedonia profiles, moderation analyses revealed that adolescents with high dmPFC neural activation in response to reward had positive relationships between social, anticipatory, and consummatory anhedonia and suicidal ideation. LIMITATIONS: Small subsample with fMRI data. CONCLUSION: Profiles of anhedonia emerge transdiagnostically and vary on clinical features. Anhedonia severity and activation in frontostriatal reward areas have value for clinically important outcomes such as suicidal ideation.

Optimizing Scripted Dialogues for an e-Health Intervention for Suicidal Veterans with Major Depression.

Suicide is a health concern among Veterans with depression. We had previously reported on scripted dialogues adapted for an e-health system that engages at-risk veterans with schizophrenia. Here we report a further adaptation of the dialogues for Veterans with depression. Usability was assessed with nine outpatients with a history of major depression and suicidality. We noted that participants preferred greater specificity in the wording of questions. Topics that elicited an emotional response dealt with questions on suicide, social isolation and family relationships. Based on feedback, dialogues were revised for patients with depression. We also compared responses between those with depression and those with schizophrenia who were previously tested. The two groups shared similar themes. Also, individuals with a history of major depression had less trouble with vocabulary comprehension but were less willing to answer more questions daily.

Using problem solving therapy to treat veterans with subsyndromal depression: a pilot study.

OBJECTIVE: We conducted a pilot study comparing problem solving therapy for primary care (PST-PC) to a dietary education control condition in middle-aged and older veterans with symptoms of emotional distress and subsyndromal depression. METHODS: This was a two-site study at the VA Pittsburgh Healthcare System and Philadelphia VA Medical Center. Participants included veterans >50 years of age referred from primary care clinics who were eligible if they obtained a pre-screen score >11 on the Centers for Epidemiologic Studies Depression (CES-D) scale. Exclusions were a DSM-IV Major Depressive Episode within the past year, active substance abuse/dependence within 1 month, current antidepressant therapy, and a Mini mental status exam score <24. Participants were randomized to receive one of two interventions--either PST-PC or an attention control condition consisting of dietary education (DIET)--each consisting of six to eight sessions within a 4-month period. RESULTS: Of 45 individuals randomized, 23 (11 PST-PC and 12 DIET) completed treatment. Using regression models in completers that examined outcomes at end of treatment while controlling for baseline scores, there were significant differences between treatment groups in SF-36 mental health component scores but not in depressive symptoms (as assessed with either the 17-item Hamilton Rating Scale for Depression or the Beck Depression Inventory), social problem solving skills, or physical health status (SF-36 physical health component score). CONCLUSIONS: These pilot study findings suggest that a six-to-eight session version of PST-PC may lead to improvements in mental health functioning in primary care veterans with subsyndromal depressive symptoms.

Development of a recovery manual for suicidal patients with schizophrenia: consumer feedback.

A recovery-oriented manual was developed for patients with schizophrenia and suicidality. It included psychoeducational information, vignettes, "workbook" sections and was reviewed by experts in suicidology, recovery, patient education, manual development and psychosocial interventions. The revised version was tested in 22 consumers with schizophrenia and a history of suicidality. Consumer-based focus groups yielded five key themes which were used to further refine the manual. A satisfaction survey indicated that 85% stated the manual was 'somewhat easy', 'easy' or 'very easy to read.' All stated it was 'very useful', 'useful' or 'somewhat useful. Thus, the manual appears to be acceptable and useful.

Dysregulation of neurosteroids in obsessive compulsive disorder.

Alterations in hormone concentrations, including adrenocorticotropin, corticotropin releasing hormone, and cortisol have been reported in patients with obsessive compulsive disorder (OCD). Dehydroepiandrosterone (DHEA) and its sulfated metabolite, DHEA-S, have not been assessed in patients with OCD. We report 24-h serum DHEA, DHEA-S, and cortisol concentrations in a young man with OCD and 15 healthy young men. Circadian patterns of DHEA and cortisol were markedly different in the subject with OCD than in the control subjects. DHEA and DHEA-S concentrations were substantially higher in the OCD subject than in the control subjects. In contrast, cortisol concentrations were similar in the OCD subject and the control subjects. Future clinical studies are needed to evaluate the significance of DHEA and DHEA-S in OCD.

A Clinical Trial to Test the Feasibility of a Telehealth Psychoeducational Intervention for Persons With Schizophrenia and Their Families: Intervention and 3-Month Findings.

OBJECTIVE: To evaluate the feasibility of a telehealth psychoeducation intervention for persons with schizophrenia and their family members. STUDY DESIGN: Randomized controlled trial. PARTICIPANTS: 30 persons with schizophrenia and 21 family members or other informal support persons. INTERVENTIONS: Web-based psychoeducation program that provided online group therapy and education. MAIN OUTCOME MEASURES: Measures for persons with schizophrenia included perceived stress and perceived social support; for family members, they included disease-related distress and perceived social support. RESULTS: At 3 months, participants with schizophrenia in the intervention group reported lower perceived stress (p = .04) and showed a trend for a higher perceived level of social support (p = .06). CONCLUSIONS: The findings demonstrate the feasibility and impact of providing telehealth-based psychosocial treatments, including online therapy groups, to persons with schizophrenia and their families.

The relationship of childhood abuse to impulsivity and suicidal behavior in adults with major depression.

OBJECTIVE: This study investigated whether a higher frequency of reported childhood trauma would be found in depressed adults with higher levels of trait impulsivity, aggression, and suicidal behavior. METHOD: In 136 depressed adult inpatients, the authors assessed trait impulsivity, aggression history, and number of lifetime suicide attempts as well as the medical lethality and the intent to die associated with the most lethal attempt. These variables were then compared between those with and those without a reported history of childhood physical or sexual abuse. RESULTS: Subjects who reported an abuse history were more likely to have made a suicide attempt and had significantly higher impulsivity and aggression scores than those who did not report an abuse history. Impulsivity and aggression scores were significantly higher in subjects with a history of at least one suicide attempt. A logistic regression analysis revealed that abuse history remained significantly associated with suicide attempt status after adjustment for impulsivity, aggression history, and presence of borderline personality disorder. Among those who attempted suicide, there were no significant differences in severity of suicidal behavior between those with and without a childhood history of abuse. CONCLUSIONS: Abuse in childhood may constitute an environmental risk factor for the development of trait impulsivity and aggression as well as suicide attempts in depressed adults. Alternatively, impulsivity and aggression may be inherited traits underlying both childhood abuse and suicidal behavior in adulthood disorders. Additional research is needed to estimate the relative contributions of heredity and environmental experience to the development of impulsivity, aggression, and suicidal behavior.

Delusions and suicidality.

OBJECTIVE: Delusions have been considered a risk factor for suicidal behavior. To determine whether specific delusion types are related to suicidal behaviors, the authors compared the clinical characteristics of patients with mood disorders and schizophrenia who did and did not have a history of suicide attempts. METHOD: After admission for inpatient or outpatient psychiatric treatment, 429 patients (ages 14-72 years; 47.1% male; and 73.0% Caucasian) were assessed with a structured clinical interview that generated axis I and II diagnoses. In addition, their psychiatric symptoms, history of suicide attempts, and overall functioning were rated. RESULTS: Data for three diagnostic subgroups (223 patients with major depression, 150 with schizophrenia, and 56 with bipolar disorder) were analyzed separately. Multivariate analyses did not find evidence of a relationship between delusions and history of suicidal ideation or suicide attempts in any of the diagnostic groups. CONCLUSIONS: This study did not find evidence that the presence of delusions distinguished persons with or without a history of suicide attempt.

Interpersonal control and expressed emotion in families of persons with schizophrenia: change over time.

This study examined communication patterns in 62 families of persons with schizophrenia, comparing families with relatives who were low expressed emotion (EE) at the beginning and end of a 2-year study, those who were high EE at the beginning and end, and those whose EE status changed. Interaction was coded with the Relational Control Coding System and analyzed as a Markov process. Dialogues in the stable low-EE and stable high-EE families were rather similar initially, and both groups showed increasing flexibility at year 1. However, at year 2, low-EE dyads showed increasingly complex structure and flexibility in control, but high-EE dyads showed simpler structure and rigidly controlling patterns. When EE status changed, so did the structure of the dialogues and the patterning of control. Although earlier research found more "tightly joined" systems in families of high-EE relatives, it may be that over time, these family members distance from each other and so are less connected. It is also possible that relatives who remain high EE despite intervention are a subset of high-EE relatives who need more support or different therapeutic approaches to maintain change.

Effects of behavioural family management on family communication and patient outcomes in schizophrenia.

BACKGROUND: Family interventions for schizophrenia have proved to be highly effective in preventing relapse, but it is not clear how they work or how they should be structured. AIMS: To examine the effects of a behavioural family intervention and a family support programme on communication, problem solving and outcome in order to determine the impact of structured communication training. METHOD: Patients and family members participating in the Treatment Strategies in Schizophrenia study were videotaped engaging in 10-minute problem-solving conversations at baseline and after the conclusion of the family intervention. Tapes were subsequently evaluated for changes in communication patterns. RESULTS: The intensive behavioural intervention did not produce differential improvement in communication, and change in communication was unrelated to patient outcomes. CONCLUSIONS: The data suggest that intensive behavioural family interventions may not be cost efficient, and that change in family communication patterns may only be important for a subset of families.

Suicidal behavior in bipolar mood disorder: clinical characteristics of attempters and nonattempters.

OBJECTIVE: Bipolar Disorder is associated with a higher frequency of attempted suicide than most other psychiatric disorders. The reasons are unknown. This study compared bipolar subjects with a history of a suicide attempt to those without such a history, assessing suicidal behavior qualitatively and quantitatively, and examining possible demographic, psychopathologic and familial risk factors. METHODS: Patients (ages 18 to 75) with a DSM III-R Bipolar Disorder (n = 44) diagnosis determined by a structured interview for Axis I disorders were enrolled. Acute psychopathology, hopelessness, protective factors, and traits of aggression and impulsivity were measured. The number, method and degree of medical damage was assessed for suicide attempts, life-time. RESULTS: Bipolar suicide attempters had more life-time episodes of major depression, and twice as many were in a current depressive or mixed episode, compared to bipolar nonattempters. Attempters reported more suicidal ideation immediately prior to admission, and fewer reasons for living even when the most recent suicide attempt preceded the index hospitalization by more than six months. Attempters had more lifetime aggression and were more likely to be male. However, attempters did not differ from nonattempters on lifetime impulsivity. LIMITATIONS: The generalizability of the results is limited because this is a study of inpatients with a history of suicide attempts. Patients with Bipolar I and NOS Disorders were pooled and a larger sample is needed to look at differences. We could not assess psychopathology immediately prior to the suicide attempt because, only half of the suicide attempters had made attempts in the six months prior to admission. Patients with current comorbid substance abuse were excluded. No suicide completers were studied. CONCLUSIONS: Bipolar subjects with a history of suicide attempt experience more episodes of depression, and react to them by having severe suicidal ideation. Their diathesis for acting on feelings of anger or suicidal ideation is suggested by a higher level of lifetime aggression and a pattern of repeated suicide attempts.

Protective factors against suicidal acts in major depression: reasons for living.

OBJECTIVE: Over 30,000 people a year commit suicide in the United States. Prior attempted suicide and hopelessness are the most powerful clinical predictors of future completed suicide. The authors hypothesized that "reasons for living" might protect or restrain patients with major depression from making a suicide attempt. METHOD: Inpatients with DSM-III-R major depression were assessed for depression, general psychopathology, suicide history, reasons for living, and hopelessness. Of the 84 patients, 45 had attempted suicide and 39 had not. RESULTS: The depressed patients who had not attempted suicide expressed more feelings of responsibility toward family, more fear of social disapproval, more moral objections to suicide, greater survival and coping skills, and a greater fear of suicide than the depressed patients who had attempted suicide. Scores for hopelessness, subjective depression, and suicidal ideation were significantly higher for the suicide attempters. Reasons for living correlated inversely with the combined score on these measures, considered an indicator of "clinical suicidality." Neither objective severity of depression nor quantity of recent life events differed between the two groups. CONCLUSIONS: During a depressive episode, the subjective perception of stressful life events may be more germane to suicidal expression than the objective quantity of such events. A more optimistic perceptual set, despite equivalent objective severity of depression, may modify hopelessness and may protect against suicidal behavior during periods of risk, such as major depression. Assessment of reasons for living should be included in the evaluation of suicidal patients.

Recent life events, social adjustment, and suicide attempts in patients with major depression and borderline personality disorder.

This study investigated the impact of recent life events and social adjustment on suicide attempter status in 34 patients with major depression, 24 patients with borderline personality disorder, and 22 patients with co-morbid major depression and borderline personality disorder. Suicide attempters reported more recent life events and scored lower on a measure of social adjustment in their families and overall social adjustment, compared with non-attempters. Borderline disordered and borderline or depressed patients were more likely to have attempted suicide than patients with major depression only. Recent life events did not predict attempter status. Lower social adjustment in the immediate family and lower overall social adjustment were predictive of suicide attempter classification, regardless of diagnosis. Borderline disordered patients low on overall social adjustment were over 16 times more likely to have attempted suicide than patients diagnosed with major depression only. Recent life events may elevate suicide risk in groups already at high risk for suicide completion, whereas high levels of social adjustment may be protective against stress-related suicidal behavior.

Suicidal behavior in patients with schizophrenia and other psychotic disorders.

OBJECTIVE: Patients with schizophrenia are known to be at high risk for suicide attempts and dying by suicide. However, little research has been conducted to determine whether the risk for suicidal behavior is elevated among patients with psychosis in general. METHOD: This study evaluated 1-month and lifetime rates of suicidal behavior among 1,048 consecutively admitted psychiatric inpatients (ages 18 to 55 years) with DSM-III-R psychotic disorders. Demographic, clinical, and diagnostic correlates of suicidal behavior were examined. RESULTS: A high rate of suicidal behavior was found in the group: 30.2% reported a lifetime history of suicide attempts, and 7.2% reported a suicide attempt in the month before admission. The highest 1-month and lifetime rates were found in patients with schizoaffective disorder and major depression with psychotic features. Ratings of the medical dangerousness of the most recent suicide attempt on the basis of the extent of physical injury were higher in patients with schizophrenia spectrum psychoses. Agreement was high between emergency room assessments and semistructured interview assessments of suicidal behavior. CONCLUSIONS: Rates of suicidal behavior were high across a broad spectrum of patients with psychotic disorders; patients with a history of a current or past major depressive episode (as a part of major depressive disorder or schizoaffective disorder) were at a greater risk for suicide attempts, but patients with schizophrenia, on average, made more medically dangerous attempts. Risk factors for suicidal behavior in patients with psychosis appear to vary compared to those for the general population.

Pursuit tracking impairments in schizophrenia and mood disorders: step-ramp studies with unmedicated patients.

BACKGROUND: Eye tracking abnormalities are highly prevalent in schizophrenia, and are among the most promising phenotypic familial markers for the disorder. The neurophysiologic mechanisms underlying these disturbances and their diagnostic specificity for schizophrenia are not yet well characterized. METHODS: This study assessed eye tracking deficits using foveopetal and foveofugal step-ramp tasks (ramps moving toward and away from central fixation after an initial step respectively) across a range of target velocities in anti-psychotic-naive schizophrenia patients, previously treated but currently unmedicated chronic schizophrenia patients, unmedicated patients with either bipolar or unipolar mood disorders, and healthy volunteers. RESULTS: All patient groups demonstrated reduced pursuit gain in open loop and closed loop visual tracking conditions. There were no significant group differences in the latency or accuracy of catch-up saccades on foveofugal ramp tasks. CONCLUSIONS: These findings indicate that open and closed loop pursuit eye movements are impaired during acute episodes of schizophrenia and mood disorders. The intact accuracy of saccades to moving targets in all patient groups indicates that an adequate representation of motion information is available to the saccade system. Therefore, pursuit disturbances in mood disorders and schizophrenia seem to result, at least in part, from a disturbance in sensorimotor integration in the pursuit system after the initial extraction of sensory motion information. No eye movement abnormalities observed during performance of step ramp tasks were specific to schizophrenia.

Landmark-based morphometric analysis of first-episode schizophrenia.

BACKGROUND: The goal of this investigation was to utilize landmark-based shape analysis and image averaging to determine the sites and extent of specific structural changes in first-episode schizophrenia. METHODS: Neuroanatomic structures identified on midsagittal magnetic resonance imaging (MRI) scans were compared between 20 patients with schizophrenia and 22 normal control subjects. The difference between averaged landmark configurations in the two groups was visualized as a shape deformation by a thin-plate spline and through averaged MRI images for both groups. RESULTS: A shape difference was found to be statistically significant; by inspection, it is contrast between differences in two closely abutting regions, involving primarily the posterior corpus callosum and upper brain stem--the "focus" is the relation between them. CONCLUSIONS: The findings are consistent with prior studies suggesting involvement in schizophrenia of the corpus callosum and the limbic structures contributing to the corpus callosum; the possibility of local pathology primarily involving the brain stem cannot be excluded. The methods of landmark-based shape analysis and image averaging utilized in this study can complement the "region-of-interest" method of investigating morphometric abnormalities by characterizing the spatial relationships among structural brain abnormalities in schizophrenia.

Prefrontal cortical dysfunction in depression determined by Wisconsin Card Sorting Test performance.

OBJECTIVE: Neuroimaging studies have demonstrated reduced prefrontal cortical blood flow and metabolism in depression, but the neurobehavioral significance of these observations is not yet established. METHOD: The Wisconsin Card Sorting Test, a widely used neuropsychological index of prefrontal cortical function, was administered to 79 patients with major depression who had been unmedicated for at least 28 days, to 47 patients with schizophrenia who had never received antipsychotic medication, and to 61 healthy comparison subjects. RESULTS: Depressed patients demonstrated significant deficits on multiple Wisconsin Card Sorting Test measures compared with healthy individuals. These deficits were correlated with the severity of depression and were less severe than those demonstrated by patients with schizophrenia. CONCLUSIONS: These results provide neuropsychological evidence for significant prefrontal cortical dysfunction in depression.

Toward a clinical model of suicidal behavior in psychiatric patients.

OBJECTIVE: Risk factors for suicide attempts have rarely been studied comprehensively in more than one psychiatric disorder, preventing estimation of the relative importance and the generalizability of different putative risk factors across psychiatric diagnoses. The authors conducted a study of suicide attempts in patients with mood disorders, psychoses, and other diagnoses. Their goal was to determine the generalizability and relative importance of risk factors for suicidal acts across diagnostic boundaries and to develop a hypothetical, explanatory, and predictive model of suicidal behavior that can subsequently be tested in a prospective study. METHOD: Following admission to a university psychiatric hospital, 347 consecutive patients who were 14-72 years old (51% were male and 68% were Caucasian) were recruited for study. Structured clinical interviews generated axis I and axis II diagnoses. Lifetime suicidal acts, traits of aggression and impulsivity, objective and subjective severity of acute psychopathology, developmental and family history, and past substance abuse or alcoholism were assessed. RESULTS: Objective severity of current depression or psychosis did not distinguish the 184 patients who had attempted suicide from those who had never attempted suicide. However, higher scores on subjective depression, higher scores on suicidal ideation, and fewer reasons for living were reported by suicide attempters. Rates of lifetime aggression and impulsivity were also greater in attempters. Comorbid borderline personality disorder, smoking, past substance use disorder or alcoholism, family history of suicidal acts, head injury, and childhood abuse history were more frequent in suicide attempters. CONCLUSIONS: The authors propose a stress-diathesis model in which the risk for suicidal acts is determined not merely by a psychiatric illness (the stressor) but also by a diathesis. This diathesis may be reflected in tendencies to experience more suicidal ideation and to be more impulsive and, therefore, more likely to act on suicidal feelings. Prospective studies are proposed to test this model.

Racial and gender differences in expressed emotion and interpersonal control in families of persons with schizophrenia.

Expressed Emotion (EE) has been shown to be predictive of course or severity in many illnesses, but the studies have been largely of white middle-class patients. This study examined gender and racial differences in parental EE level and communication patterns between the parent and patient with schizophrenia, using data from the NIMH Treatment Strategies in Schizophrenia study. Dialogues (n = 140) from 54 patient-parent dyads were coded into the Relational Control Coding System. Resultant data (n = 13,605 sequences) were analyzed with log-linear models. Results show that the relationship between control and EE level was stronger in African American families compared to Caucasians. Gender differences were as expected, with daughters less competitive and more deferential to their parents. Although the total number of high-EE parents with daughters was small, patterns in these families showed parents who responded submissively in contrast to the competitive symmetry in families with male patients.

Eye tracking abnormalities in schizophrenia: evidence for dysfunction in the frontal eye fields.

BACKGROUND: Eye tracking deficits are robust abnormalities in schizophrenia, but the neurobiological disturbance underlying these deficits is not known. METHODS: To clarify the pathophysiology of eye tracking disturbances in schizophrenia, we tested 12 first-episode treatment-naive schizophrenic patients and 10 matched healthy individuals on foveofugal and foveopetal step-ramp pursuit tasks. RESULTS: On foveopetal tasks, the initiation of pursuit eye movements was delayed in schizophrenic patients, and their steady-state pursuit gain was reduced particularly at slower target speeds (8 and 16 deg/sec). In foveofugal step-ramp tasks, their primary catch-up saccades were normal in latency and accuracy, but their postsaccadic pursuit in the first 100 msec after the primary catch-up saccade was significantly reduced even relative to their slow steady-state pursuit, especially during and immediately after an acute episode of illness. CONCLUSIONS: These observations indicate that motion-sensitive areas in posterior temporal cortex provide sufficiently intact information about moving targets to guide accurate catch-up saccades, but that the sensory processing of motion information is not being used effectively for pursuit eye movements. Low-gain pursuit after the early stage of pursuit initiation suggests that the use of extraretinal signals about target motion (e.g., anticipatory prediction) only partially compensates for this deficit. The pattern of low-gain pursuit, impaired pursuit initiation, and intact processing of motion information for catch-up saccades but not pursuit eye movements, was consistent in the schizophrenic patients tested at five time points over a 2-year follow-up period, and implicates the frontal eye fields or their efferent or afferent pathways in the pathophysiology of eye tracking abnormalities in schizophrenia.