Dysregulated brain development in adult men with schizophrenia: a magnetic resonance imaging study.

BACKGROUND: Recent imaging evidence suggests that normal brain development/maturation of the frontal lobes and association areas is a well-regulated process consisting of continued myelination and expansion of white matter volumes into the late 40s accompanied by complementary reductions in gray matter volumes. The possibility that a dysregulation of this process may contribute to the syndrome of schizophrenia was investigated using magnetic resonance imaging. METHODS: Fifty-two normal adult males and 35 males with schizophrenia underwent magnetic resonance imaging. Coronal images were acquired using pulse sequences that maximized myelin signal. The age-related change in the gray to white matter ratio was used as a measure of developmental dysregulation in the schizophrenic subjects and contrasted to the age-related changes of the normal control group. RESULTS: Regression analyses on frontal and temporal gray to white matter ratio yielded highly significant interactions of diagnosis and age for both regions (p =.0003 and p =.01, respectively). In the normal group, both frontal and temporal gray to white matter ratios decreased significantly and linearly across the age range. In contrast, neither ratio showed meaningful age-related change in the schizophrenia group. Thus, differences in gray to white matter ratio between the groups increased markedly with age, driven primarily by the absence of a white matter volume expansion in the patient group. CONCLUSIONS: The absence of the normal complementary volume changes in the gray and white matter with age in the schizophrenic sample suggests that this dynamic developmental process is dysregulated in adult schizophrenic subjects. The importance of myelination to the continued maturation and normal functioning of the brain has implications for the diagnosis, treatment, and prognosis of schizophrenia.     

Trait versus state aspects of the MMPI during the early course of schizophrenia.

Scores on the Minnesota Multiphasic Personality Inventory (MMPI)-168 item version were examined during periods of clinical remission and of psychosis for recent-onset schizophrenia patients (n = 19) and at comparable time intervals for demographically matched normal participants (n = 19). To determine diagnostic specificity, MMPIs for participants with bipolar affective disorder in remission (n = 12) were also examined. Methods for distinguishing between stable vulnerability indicators, mediating vulnerability factors and episode indicators of psychopathology were adapted from Nuechterlein and Dawson (1984). MMPI scales Pa, Sc and validity scale F showed a combination of trait and state qualities, characteristic of mediating vulnerability factors. These scales reflect changes that occur during psychotic episodes but also apparently tap personality characteristics that endure into periods of clinical remission. Unexpectedly, some MMPI scales that are not typically associated with psychotic disorders (i.e. Hs, D, and Hy) were significantly higher in schizophrenia patients across psychotic and clinically remitted states than in normal participants. In clinical remission, higher scores on scales Hs, D and Hy, showed some specificity to schizophrenia relative to bipolar disorder. While MMPI-168 scales Pd and Pt fit the pattern for vulnerability indicators, it was uncertain whether they belonged to the 'stable' versus 'mediating' subtype. MMPI scores that continue to be higher in remission than in a normal sample may reflect either enduring vulnerability factors or the impact of schizophrenia and the individuals' attempts to cope with the disorder. Studies of first-degree relatives will be needed to provide converging evidence that certain personality characteristics reflect genetic predisposition to schizophrenia.     

Forward and backward visual masking in unaffected siblings of schizophrenic patients.

BACKGROUND: Visual masking tasks assess the earliest stages of visual processing. This study examined visual masking performance for forward and backward masking tasks in siblings of schizophrenic patients and healthy comparison subjects. METHODS: A staircase method was used to ensure that unmasked target identification was equivalent across subjects to eliminate differences due to discrimination of simple perceptual inputs. Four computerized visual masking tasks were administered to 43 siblings of patients and 42 normal comparison subjects. The tasks included: 1) locating a target; 2) identifying a target with a high-energy mask; 3) identifying a target with a low-energy mask; and 4) a paracontrast/metacontrast procedure with nonoverlapping target and mask. RESULTS: Across masking conditions, there was a significant group by forward/backward interaction, meaning that siblings showed a larger difference from control subjects in backward versus forward masking. This group difference was more pronounced in the location condition. CONCLUSIONS: These results support the theory that visual masking procedures may be indicators of vulnerability to schizophrenia. The pattern of findings in this report (larger group differences on backward versus forward masking and on the location condition) suggests that the activity of transient visual channels may be particularly linked to vulnerability.     

Interrater reliability of the Structured Clinical Interview for DSM-III-R, Axis II: schizophrenia spectrum and affective spectrum disorders.

Three interviewers (second raters) blindly rated 15 audiotapes each of the Structured Clinical Interview for DSM-III-R, Axis II (SCID-II) administered to the first degree relatives of probands with either DSM-III-R schizophrenia, schizoaffective disorder, or bipolar disorder, for a total of 45 second ratings. Interrater reliability was determined using the intraclass correlation coefficient and ranged from 0.60 to 0.84. The previous studies of the reliability of structured interviews for diagnosing personality disorders are summarized and compared to the present findings. We conclude that the SCID-II can be reliably used to diagnose schizophrenia-spectrum and affective spectrum disorders in the first degree family members of probands with schizophrenic or bipolar affective disorders.     

The temporal relationship between depressive and psychotic symptoms in recent-onset schizophrenia

The authors examined the temporal relationship between onset of depressive and psychotic symptoms in 27 patients with recent-onset schizophrenia or schizo-affective disorder. Ratings on the Brief Psychiatric Rating Scale were collected every 2 weeks for at least 1 year to specify onset of relapse or exacerbation. Six time periods were defined in relation to onset of psychotic symptoms, and the number of depressive periods was determined for each time period. Onset of depressive periods was concurrent with onset of psychosis more often than expected but was not associated with any other time period. The authors found no distinctive postpsychotic pattern of onset for depression.     

The puzzle of schizophrenia: tracking the core role of cognitive deficits

Cognitive deficits in schizophrenia are increasingly accepted as core features of this disorder that play a role as vulnerability indicators, as enduring abnormalities during clinical remission, and as critical rate-limiting factors in functional recovery. This article demonstrates the lasting influence of Norman Garmezy through his impact on one graduate student and then through his later collaborative research with colleagues. The promise of core cognitive deficits as vulnerability indicators or endophenotypes was demonstrated in research with children born to a parent with schizophrenia as well as with biological parents and siblings of individuals with schizophrenia. In studies of patients with a recent onset of schizophrenia, cognitive deficits were found to endure across psychotic and clinically remitted periods and to have a strong predictive influence on likelihood of returning successfully to work or school. Converging lines of evidence for the enduring core role of cognitive deficit in schizophrenia have led in recent years to a burgeoning interest in developing new interventions that target cognition as a means of improving functional recovery in this disorder.     

Symptom monitoring in the rehabilitation of schizophrenic patients

Although precise laboratory methods for measuring psychopathology are not available, interviewer-rated instruments developed to assess symptomatology can be used to monitor schizophrenic patients undergoing rehabilitation. By regularly assessing patients, rehabilitation staff can improve the effectiveness of their interventions. Patients can be screened for high levels of symptomatology which might preclude assignment to rehabilitation programs with high levels of social stimulation. Monitoring the prodromal symptoms of relapse can sometimes prevent florid relapses and sustain a rehabilitative trajectory. Standardized instruments for measuring positive symptoms (e.g., hallucinations, delusions, and conceptual disorganization) and negative symptoms (e.g., affective blunting, amotivation, and asociality) are available. Monitoring target symptoms may be particularly cost effective in the rehabilitation milieu. Use of suggested operational criteria for defining clinical states such as relapse would improve outcome studies on rehabilitation interventions.