Jolanta Zanelli

A developmental model for similarities and dissimilarities between schizophrenia and bipolar disorder

Schizophrenia and mania have a number of symptoms and epidemiological characteristics in common, and both respond to dopamine blockade. Family, twin and molecular genetic studies suggest that the reason for these similarities may be that the two conditions share certain susceptibility genes. On the other hand, individuals with schizophrenia have more obvious brain structural and neuropsychological abnormalities than those with bipolar disorder; and pre-schizophrenic children are characterised by cognitive and neuromotor impairments, which are not shared by children who later develop bipolar disorder. Furthermore, the risk-increasing effect of obstetric complications has been demonstrated for schizophrenia but not for bipolar disorder. Perinatal complications such as hypoxia are known to result in smaller volume of the amygdala and hippocampus, which have been frequently reported to be reduced in schizophrenia; familial predisposition to schizophrenia is also associated with decreased volume of these structures. We suggest a model to explain the similarities and differences between the disorders and propose that, on a background of shared genetic predisposition to psychosis, schizophrenia, but not bipolar disorder, is subject to additional genes or early insults, which impair neurodevelopment, especially of the medial temporal lobe.

Meta-analysis of magnetic resonance imaging brain morphometry studies in bipolar disorder

BACKGROUND Several studies assessing volumetric measurements of regional brain structure in bipolar disorder have been published in recent years, but their results have been inconsistent. Our aim was to complete a meta-analysis of regional morphometry in bipolar disorder as assessed using magnetic resonance imaging (MRI). METHODS We conducted a systematic literature search of MRI studies of bipolar disorder and identified studies which reported volume measurements in a selected number of regions. Twenty-six studies comprising volumetric measurements on up to 404 independent patients with bipolar disorder were included. A meta-analysis was carried out comparing the volumes of regions in bipolar disorder to comparison subjects using a random effects model. RESULTS Patients with bipolar disorder had enlargement of the right lateral ventricle, but no other regional volumetric deviations which reached significance. Strong heterogeneity existed for several regions, including the third ventricle, left subgenual prefrontal cortex, bilateral amygdala and thalamus. CONCLUSIONS Regional volume of most structures we studied is preserved in bipolar disorder as a whole, which was significantly associated only with right-sided ventricular enlargement. However the extensive heterogeneity detected indicates the need for further studies to establish if consistent regional brain volume deviation exists in bipolar disorder or in specific clinical subsets of the illness.

Specific and Generalized Neuropsychological Deficits: A Comparison of Patients With Various First-Episode Psychosis Presentations

OBJECTIVE Overwhelming evidence suggests that compromised neuropsychological function is frequently observed in schizophrenia. Neurocognitive dysfunction has often been reported in other psychotic disorders, although there are inconsistencies in the literature. In the context of four distinct diagnostic groups, the authors compared neuropsychological performance among patients experiencing their first psychotic episode. METHOD Data were derived from a population-based, case-control study of patients with first-episode psychosis. A neuropsychological test battery was administered to patients with a diagnosis of schizophrenia (N=65), bipolar disorder or mania (N=37), depressive psychosis (N=39), or other psychotic disorders (N=46) following index presentation, as well as to healthy comparison subjects (N=177). The presence of specific and generalized cognitive deficits was examined. RESULTS The schizophrenia group presented widespread neuropsychological impairments and performed significantly worse than healthy comparison subjects on most neuropsychological measures. Patients with other psychotic disorders and depressive psychosis also demonstrated widespread impairments. Deficits in patients with bipolar disorder or mania were less pervasive but evident in performance scores on verbal memory and fluency tests. Differences between the four patient groups and healthy comparison subjects and among the patient groups were attenuated after controlling for differences in general cognitive ability (IQ). CONCLUSIONS Early in their course, cognitive deficits are present in all psychotic disorders but are most severe and pervasive in schizophrenia and least pervasive in bipolar disorder and mania.

Is there a link between childhood trauma, cognition, and amygdala and hippocampus volume in first-episode psychosis?

Patients with psychosis have higher rates of childhood trauma, which is also associated with adverse effects on cognitive functions such as attention, concentration and mental speed, language, and verbal intelligence. Although the pathophysiological substrate for this association remains unclear, these cognitive deficits may represent the functional correlate of changes observed in relation to trauma exposure in structures such as the amygdala and the hippocampus. Interestingly, these structures are often reported as altered in psychosis. This study investigated the association between childhood trauma, cognitive function and amygdala and hippocampus volume, in first-episode psychosis. We investigated 83 patients with first-episode psychosis and 63 healthy controls. All participants underwent an MRI scan acquired with a GE Sigma 1.5-T system, and a standardized neuropsychological assessment of general cognition, memory, processing speed, executive function, visuo-spatial abilities, verbal intelligence, and language. In a subsample of the patients (N=45) information on childhood trauma was collected with the Childhood Experience of Care and Abuse Questionnaire (CECA.Q). We found that amygdala, but not hippocampus, volume was significantly smaller (p=0.001) in patients compared to healthy controls. There was a trend level interaction for hippocampus volume between group and sex (p=0.056). A history of childhood trauma was associated with both worse cognitive performance and smaller amygdala volume. This smaller amygdala appeared to mediate the relationship between childhood trauma and performance on executive function, language and verbal intelligence in patients with psychosis. This points to a complex relationship between childhood trauma exposure, cognitive function and amygdala volume in first-episode psychosis.

Duration of untreated psychosis and neuropsychological function in first episode psychosis.

PURPOSE We investigated whether duration of untreated psychosis (DUP) prior to first presentation was associated with cognitive function in first episode psychosis (FEP) subjects. We predicted that longer DUP would be associated with greater neurocognitive impairment. METHOD 180 subjects with schizophrenia (and 93 subjects with Other Psychoses) performed a neurocognitive battery assessing IQ, verbal learning, working memory, visual learning and speed of processing. DUP was defined as the number of days between first onset of psychotic symptoms and first contact with psychiatric services. RESULTS Longer DUP was associated with impaired performance in verbal IQ (p=0.04), verbal learning (p=0.02), and verbal working memory (p=0.04) in FEP subjects with schizophrenia. These associations remained significant for verbal IQ when scores were corrected for age, gender, educational level and ethnicity. CONCLUSIONS Longer DUP is associated with poorer neurocognitive ability in schizophrenia subjects at time of first presentation. Since this was a cross-sectional study we can not tell whether longer DUP was a cause or a consequence of the poorer performance.

Neurological abnormalities and cognitive ability in first-episode psychosis

BACKGROUND It remains unclear if the excess of neurological soft signs, or of certain types of neurological soft signs, is common to all psychoses, and whether this excess is simply an epiphenomenon of the lower general cognitive ability present in psychosis. AIMS To investigate whether an excess of neurological soft signs is independent of diagnosis (schizophrenia v. affective psychosis) and cognitive ability (IQ). METHOD Evaluation of types of neurological soft signs in a prospective cohort of all individuals presenting with psychoses over 2 years (n=310), and in a control group from the general population (n=239). RESULTS Primary (P<0.001), motor coordination (P<0.001), and motor sequencing (P<0.001) sign scores were significantly higher in people with any psychosis than in the control group. However, only primary and motor coordination scores remained higher when individuals with psychosis and controls were matched for premorbid and current IQ. CONCLUSIONS Higher rates of primary and motor coordination signs are not associated with lower cognitive ability, and are specific to the presence of psychosis.

Criminal offending and distinguishing features of offenders among persons experiencing a first episode of psychosis

Aims: Persons with severe mental illness (SMI) are at increased risk of criminal offending, particularly violent offending, as compared with the general population. Most offenders with SMI acquire convictions prior to contact with mental health services. This study examined offending among 301 individuals experiencing their first episode of psychosis.

Bilateral hippocampal increase following first-episode psychosis is associated with good clinical, functional and cognitive outcomes

BACKGROUND Hippocampal pathology has been proposed to underlie clinical, functional and cognitive impairments in schizophrenia. The hippocampus is a highly plastic brain region; examining change in volume, or change bilaterally, over time, can advance understanding of the substrate of recovery in psychosis. METHOD Magnetic resonance imaging and outcome data were collected at baseline and 6-year follow-up in 42 first-episode psychosis subjects and 32 matched controls, to investigate whether poorer outcomes are associated with loss of global matter and hippocampal volumes. Bilateral hippocampal increase (BHI) over time, as a marker of hippocampal plasticity was hypothesized to be associated with better outcomes. Regression analyses were performed on: (i) clinical and functional outcomes with grey matter volume change and BHI as predictor variables; and (ii) cognitive outcome with BHI as predictor. RESULTS BHI was present in 29% of psychosis participants. There was no significant grey matter loss over time in either patient or control groups. Less severe illness course and lesser symptom severity were associated with BHI, but not with grey matter change. Employment and global function were associated with BHI and with less grey matter loss. Superior delayed verbal recall was also associated with BHI. CONCLUSIONS BHI occurs in a minority of patients following their first psychotic episode and is associated with good outcome across clinical, functional and cognitive domains.

Linear and non-linear associations of symptom dimensions and cognitive function in first-onset psychosis

BACKGROUND Associations between symptom dimensions and cognition have been mainly studied in non-affective psychosis. The present study investigated whether previously reported associations between cognition and four symptom dimensions (reality distortion, negative symptoms, disorganisation and depression) in non-affective psychosis generalise to a wider spectrum of psychoses. It also extended the research focus to mania, a less studied symptom dimension. METHODS Linear and non-linear (quadratic, curvilinear or inverted-U-shaped) associations between cognition and the above five symptom dimensions were examined in a population-based cohort of 166 patients with first-onset psychosis using regression analyses. RESULTS Negative symptoms showed statistically significant linear associations with IQ and processing speed, and a significant curvilinear association with verbal memory/learning. Significant quadratic associations emerged between mania and processing speed and mania and executive function. The contributions of mania and negative symptoms to processing speed were independent of each other. The findings did not differ between affective and non-affective psychoses, and survived correction for multiple testing. CONCLUSIONS Mania and negative symptoms are associated with distinct patterns of cerebral dysfunction in first-onset psychosis. A novel finding is that mania relates to cognitive performance by a complex response function (inverted-U-shaped relationship). The associations of negative symptoms with cognition include both linear and quadratic elements, suggesting that this dimension is not a unitary concept. These findings cut across affective and non-affective psychoses, suggesting that different diagnostic entities within the psychosis spectrum lie on a neurobiological continuum.

Eye tracking in schizophrenia: Does the antisaccade task measure anything that the smooth pursuit task does not?

Smooth pursuit and antisaccade eye-tracking abnormalities have been proposed as endophenotypes for schizophrenia. However, it is not clear whether these tasks measure the same underlying abnormality. We hypothesised that these measures would be correlated. The association between smooth pursuit and antisaccade task performance was assessed in 50 schizophrenic patients, 80 unaffected first-degree relatives and 40 unaffected controls. Smooth pursuit measures included gain, number of saccades and a qualitative measure of smooth pursuit. The antisaccade distractibility error (ADE) score was the only measure of the antisaccade task. A significant correlation was found between reduced gain and an increased ADE score for all the subjects in the three groups combined. The total number of saccades was negatively correlated with the ADE score in the schizophrenic group, but positively in the relative group. Qualitative ratings of smooth pursuit correlated with the ADE score. Our results suggest that the antisaccade distractibility error score is related to gain and qualitative measures of smooth pursuit, although the relationship with number of saccades did not conform to this pattern. The finding may reflect a shared genetic liability, that affects both eye-tracking phenotypes. It is likely that both measures reflect frontal cortical dysfunction.