Non-invasive physiological measures of in vivo brain function, derived from positron emission tomography (PET) and functional magnetic resonance (fMRI), are now standard tools in cognitive neuroscience. These techniques provide a powerful context for addressing critical questions regarding both the localization and mechanisms of higher brain functions. A general overview of the history and development of imaging techniques in relation to cognitive science is that of Posner & Raichle (1994). The conceptual background and methodological approaches available for neurobiological based psychiatric research, in conjunction with functional imaging, provides the focus for the present review.

Major psychiatric disorders, such as schizophrenia and depression, represent disturbances at the highest level of brain function. Providing a neurobiological account of these conditions presents the most formidable problem in clinical neuroscience. Questions posed by neurobiological perspectives on psychiatric disorders are necessarily embedded in theoretical assumptions about how we think that the brain works. From this, it follows that an important limiting factor in any neurobiological account of psychiatric disease is the stage of development and theoretical conceptualization of brain function in general.

Background. Single photon emission tomography (SPET) with the dopamine D2/3 ligand 123I-IBZM gives a semi-quantitative estimate of dopamine binding. In depressed patients, we predicted evidence of reduced function, i.e. increased binding, particularly in more retarded patients.

Methods. Fifteen depressed patients with major depressive illness and 15 healthy, age- and sex-matched volunteers were examined with a clinical and neuropsychological test battery and high resolution IBZM-SPET. Estimates for specific binding were computed by averaging striatum to whole slice or frontal uptake ratios over 8–10 scans acquired from 70 min after tracer injection.

Results. Using whole slice as reference, left striatal uptake ratios did not significantly differ for patients from controls. Right ratios were significantly higher in patients than controls (P=0·03). There were significant correlations between IBZM binding in left and right striatum and measures of reaction time and verbal fluency.

Conclusions. Increased IBZM binding in striatum probably reflects reduced dopamine function, whether due to reduced release of dopamine, or secondary up-regulation of receptors. The observed abnormalities may be trait or state related, an issue that needs to be addressed with longitudinal study designs. The possible role of medication as a confounding variable requires further exploration.

Background. Many studies have separately reported abnormalities of frontal and temporal lobe structures in schizophrenia, but little is known of structural fronto-temporal associations in this condition. We investigated whether male patients with chronic schizophrenia would show abnormal patterns of correlation between regional brain volumes.

Methods. Structural magnetic resonance images of the brain in 42 patients were compared with 43 matched unaffected controls. We explored the pattern of association between regional brain volumes by correlational analyses, and non-parametrically tested for significance of between-group differences by randomization.

Results. The schizophrenics demonstrated significant volume deficits in several brain regions (left temporal lobe and hippocampus, right dorsolateral prefrontal cortex), and significant volume increases in the ventricular system (third ventricle and left temporal horn of the lateral ventricle). Controls demonstrated large positive correlations (r>0·4) between prefrontal and temporal lobe regions. By contrast, inter-regional correlations significantly reduced in schizophrenics included those between prefrontal, anterior cingulate and temporal regions, and between posterior cingulate and hippocampus (P<0·05). The most salient abnormality in patients was a dissociation between prefrontal and superior temporal gyrus volumes (P<0·01).

Conclusions. These results support the existence of a relative ‘fronto-temporal dissociation’ in schizophrenia which we suggest may be due to lack of mutually trophic influences during frontal and temporal lobe development.

Background. Previous work suggests that temporal lobe magnetic resonance imaging (MRI) can distinguish those with dementia of the Alzheimer type (DAT) from healthy age-matched controls. However, its specificity with regard to conditions such as vascular dementia, depression and other disorders associated with cognitive impairment has not been determined.

Methods. We studied 222 subjects using T1 weighted MRI with 5·1 mm coronal slices throughout the temporal lobe. Subjects included: healthy controls (N=40); DSM-III-R major depression (N=61); NINCDS/ADRDA DAT (N=77) and OTHER (N=44, comprising subjects with vascular dementia, Huntington's disease, schizophrenia, alcohol related cognitive impairment and a group of ‘memory complainers’). Hippocampus, amygdala, entorhinal cortex, parahippocampal gyrus and cerebral cortex were rated visually on a 0–3 scale by two experienced neuroradiologists blind to clinical diagnosis.

Results. Ratings of temporal lobe atrophy provided good separation between those with AD and all other groups. For example, anterior hippocampal atrophy had a sensitivity of 83% for detecting DAT, a specificity of 80% for controls, 87% for depressed subjects and 89% for OTHER. Other regions were less sensitive, but more specific for the diagnosis of DAT. In particular parahippocampal gyrus and entorhinal cortex had high specificity (97% for depressed subjects and 98% for OTHER). Because of an age-related increase in atrophy, sensitivity was highest for those over the age of 75, while specificity was highest for younger subjects. Significant correlations were observed between atrophy ratings of hippocampus, amygdala, entorhinal cortex and parahippocampal gyrus and CAMCOG memory score and length of history.

Conclusions. Temporal lobe MRI may have an important role in assisting with the clinical diagnosis of DAT, particularly its differentiation from depression and other disorders that may cause diagnostic difficulties in clinical practice.

Background. While neuropsychological studies have consistently reported impaired cognition in elderly patients with unipolar depression, studies of cognitive function in younger patients with depression have produced equivocal results. The aim of this study was to examine the presence and nature of cognitive deficits in young patients with depression.

Methods. Neuropsychological function was assessed in 20 young patients with unipolar depression, in comparison to 20 age-, education- and IQ- matched controls. Subtests from the Cambridge Neuropsychological Test Automated Battery (CANTAB) were employed, as this battery has proved sensitive to deficits in middle-aged and elderly patients with depression.

Results. The patients were not impaired for short-term memory capacity, spatial working memory, planning ability, cognitive speed, delayed matching to sample or recognition memory. Compared to controls, the patients showed impaired subsequent movement latencies on the Tower of London task, suggesting deficits in the ability to sustain motor responses in depression. The depression group were also impaired on the task of attentional set shifting, requiring more trials to criterion at the intradimensional stage of the task and being more likely to fail the task at the extradimensional shift stage than controls. Further analysis indicated that half of the depression group failed to complete all stages of the set shifting task. These patients were more likely to have required in-patient hospitalization at some time during their illness.

Conclusions. These results indicate that there are specific cognitive deficits in young patients with depression and that their presence may be related to a history of hospitalization.

Background. We investigated whether schizophrenic subjects are impaired in non-routine behaviour because of the dysfunction of a general executive component labelled, in neuropsychological terms, the supervisory system.

Methods. A specific verbal sequencing test was designed for this purpose. Subjects had to perform sequential reasoning with verbal material. Each test sequence consisted of a series of words presented in jumbled order. The construction of some sequences had to be done using familiar routine associations (valid conditions). In contrast, some other sequences required the overriding selection of familiar routine associations, which were inappropriate within the general context of the task (invalid conditions). Twenty verbal sequences (10 valid–10 invalid) were administered. Thirty-seven DMS-IV schizophrenic patients and 21 normal volunteers matched for age and educational level were recruited.

Results. Compared to the control group the schizophrenic group was impaired in both valid and invalid conditions. The number of ‘capture errors’ specific to supervisory system failure was significantly higher in the schizophrenic group and only the schizophrenic patients had significantly fewer correct sequences in invalid conditions than in valid conditions. Poor performance in invalid conditions alone was observed only among the schizophrenic subjects without a general cognitive defect.

Conclusions. These findings suggest that sequencing procedures requiring an executive input are impaired in schizophrenia.

Background. The disorganization pattern in schizophrenia, which involves formal thought disorders, is thought to be correlated with a deficit in integrative processes of contextual information. We tested the hypothesis that thought disordered schizophrenics, unlike non-thought disordered schizophrenics, would present a deficit in the processing of the context during a task which involves these integrative processes.

Methods. A group of 22 schizophrenic patients diagnosed in accordance with DSM-III-R criteria and a group of 11 control subjects were compared using a semantic priming version of the lexical decision task. The experimental design used low-level structuration of verbal material to reveal the difficulty that schizophrenic patients encounter in using semantic regularities.

Results. A significant difference in priming effect was found between the three groups. Control subjects and non-thought disordered schizophrenics exhibit a priming effect for related word pairs when compared with unrelated pairs (respectively F(1,10)=17·7; P<0·002 and F(1,10)=14·5; P>0·003) but thought disordered schizophrenics did not (F(1,10)<1; NS).

Conclusions. This finding provides evidence for the cognitive heterogeneity of schizophrenic subjects. This absence of priming effect in thought-disordered schizophrenic subjects supports the hypothesis that these patients present a deficit in the post-lexical controlled information processing that permits the integration of semantic information.

Background. It has been suggested that the expression of psychosis may reflect an active morbid process that is associated with increasingly poor outcome unless ameliorated by antipsychotic drugs.

Methods. The subjects of this study were 48 in-patients with schizophrenia, many of whom had been admitted before the introduction of antipsychotic drugs to rural Irish psychiatric hospitals in the late 1950s. Each patient was assessed for positive and negative symptoms, and for general and executive (frontal) cognitive function.

Results. After controlling for age and for duration and continuity of subsequent antipsychotic treatment, current severity both of negative symptoms and of general cognitive impairment was predicted strongly by increasing duration of initially untreated psychosis; duration of illness following initiation of antipsychotic medication failed to predict the severity thereof. Neither of these indices of illness duration predicted the severity of positive symptoms or of executive dyscontrol.

Conclusions. Increasing duration of initially untreated psychosis was associated specifically with heightened accrual of prominent negative symptoms and general cognitive impairment. Executive dyscontrol, though also prominent in these patients, may be ‘locked-in’ at an earlier phase of the illness.

Background. This study aimed to quantify the association between low IQ and the later development of psychosis in a population-based cohort study of 18-year-old conscripts.

Methods. Fifty thousand males conscripted into the Swedish army in 1969–1970 were followed by means of the Swedish National Register of Psychiatric Care up to 1983. Tests of verbal and visuospatial abilities, general and mechanical knowledge and several psychosocial variables were recorded at conscription.

Results. One hundred and ninety-five subjects were admitted to hospital with schizophrenia and 192 with a non-schizophrenic psychosis on ICD-8 criteria. The distribution of scores in those later diagnosed as suffering from schizophrenia was shifted in a downward direction, with a linear relationship between low IQ and risk. This remained after adjustment for potential confounders. The risk for non-schizophrenic disorders was also higher in those with lower IQ but the effect was less marked and non-linear. Only poorer performance on the verbal tasks and mechanical knowledge test conferred a significantly increased risk for schizophrenia after taking into account general intellectual ability. Low IQ at conscription was not related to age of onset.

Conclusions. The results confirm the importance of low intellectual ability as a risk factor for schizophrenia and other psychoses. This is unlikely to be due to prodromal decline or known confounders. The association could be directly causal with cognitive impairment leading to false beliefs and perceptions, or could be indirect with any factors causing lower IQ, such as abnormal brain development increasing the risk for schizophrenia.

Background. There has been a widespread development of community multi-disciplinary teams aimed to deliver coordinated comprehensive mental health care, yet there is little published evidence on the quality of care and economics of providing such care for people with severe mental illness.

Method. This is a clustered randomized controlled economic comparison of the quality of care for patients with chronic schizophrenia by a multi-disciplinary community team with close links with primary care, and a traditional psychiatric service in a district general hospital psychiatric unit.

Results. Two years after it was established, patients with access to the community team had more of their needs met; they had fewer unmet needs; and they were more satisfied with the care they had received. They had more service contacts and received more interventions. The community team resulted in savings in the use of some hospital resources but these were not sufficient to offset the cost of the new service. The community team successfully directed care to patients with more needs, whereas no such relationship was evident for the traditional hospital-based service. Four years after the team was established, it met a greater proportion of needs for underactivity, daily living skills, use of public amenities and managing finances.

Conclusions. Better quality care was provided at 2 and 4 years after its establishment by the multi-disciplinary community service than the traditional hospital-based service. Resources were targeted more efficiently by the community service.

Background. A number of recent epidemiological studies have shown that the prevalence and incidence of dementia are increased in population strata with low compared to high levels of education. This has been explained as a consequence of a greater ‘brain reserve capacity’ in people with a high level of education. Theoretically, however, brain reserve capacity is better reflected by intelligence than by level of education. Thus, the emergence of dementia will be better predicted by low pre-morbid intelligence than by low education.

Methods. This prediction was tested in a population based sample of elderly subjects (N=2063; age range 65–84; Amsterdam Study of the Elderly) who were followed over 4 years. Dementia was diagnosed using the Geriatric Mental State examination (GMS). Pre-morbid intelligence was measured using the Dutch Adult Reading Test (DART), a short reading test which gives a good estimate of verbal intelligence, and is relatively insensitive to brain dysfunction. The effects of age, gender, occupational level, number of diseases affecting the central nervous system and family history of dementia or extreme forgetfulness were also examined.

Results. Logistic regression analysis showed that low DART-IQ predicted incident dementia better than low level of education. A high occupational level (having been in charge of subordinates) had a protective effect.

Conclusions. This result supports the brain reserve theory. It also indicates that low pre-morbid intelligence is an important risk factor for cognitive decline and dementia. Use of reading ability tests is to be preferred over years of education as estimator of pre-morbid cognitive level in (epidemiological) dementia research.

Background. A preliminary report by the authors suggested that the range of affect generated by voices (anger, fear, elation) was linked not to the form, content or topography of voice activity, but to the beliefs patients held about them, in particular their supposed power and authority. We argued that this conformed to a cognitive model; that is, voice beliefs represent an attempt to understand the experience of voices, and cannot be understood by reference to the form/content of voices alone. This study puts this cognitive model to empirical test.

Methods. Sixty-two voice hearers conforming to ICD-10 schizophrenia or schizoaffective diagnoses were interviewed and completed standardized measures of voice activity; beliefs about voices and supporting evidence, coping behaviour; affect and depression.

Results. Beliefs about the power and meaning of voices showed a close relationship with coping behaviour and affect (malevolent voices were associated with fear and anger and were resisted; benevolent voices were associated with positive effect and were engaged) and accounted for the high rate of depression in the sample (53%). Measures of voice form and topography did not show any link with behaviour or affect and in only one-quarter of cases did neutral observers rate voice beliefs as ‘following directly’ from voice content.

Conclusion. The study found support for our cognitive model and therapeutic approach. Factors governing the genesis of these key beliefs remain unknown. A number of hypotheses are discussed, which centre around the possibility that voice beliefs develop as part of an adaptive process to the experience of voices, and are underpinned by core beliefs about the individuals self-worth and interpersonal schemata.

Background. It is widely believed that for the severely mentally ill continuity of care is essential to ensure a better outcome and prevent long-term hospitalization. However, not much progress has been made in the operationalization and measurement of this concept. We used two indicators to compare continuity of care of schizophrenic patients in two kinds of mental health systems. One is a community mental health system without the back-up of a mental hospital (South-Verona, Italy). The other is an institution-based system in which mental hospitals are still predominant (Groningen, The Netherlands).

Methods. The first indicator of continuity of care, readiness of aftercare, is the time from discharge from hospital to the first day- or out-patient contact. Survival analysis was applied to correct for censored observations. The second indicator, flexibility of care, is the use of combinations of in-, day- and out-patient care during 2-year follow-up.

Results. More patients in South-Verona received community care within 2 weeks after discharge (71·5%), than in the Groningen register area (54·6%). The survival functions differed significantly. Cox regression analysis revealed that in both systems a contact before admission, the time between this contact and admission and the duration of the admission are predictors for aftercare. A higher percentage of patients made multiple service use (combinations of in-, day- and out-patient care) in South-Verona than in Groningen (62 v. 45%).

Conclusions. Both indicators showed a higher continuity of care in the South-Verona system.

Background. An initial prevalence survey of mental disorders among 993 subjects aged 15 and above randomly drawn from four major Taiwanese aboriginal groups (the Atayal, Ami, Bunun and Paiwan) was conducted from 1986 to 1988. The incidence of alcoholism was investigated in a follow-up survey from 1990 to 1992.

Methods. Both surveys employed a semi-structured clinical interview with satisfactory reliability for case identification, and DSM-III-R as the diagnostic criteria for alcohol use disorders. The estimation of incidence rates of first onset alcoholism (alcohol abuse or dependence) was based on person-years at risk of 499 subjects who did not have any lifetime diagnosis of such morbidity at phase I.

Results. The follow-up rate was 99·6% and only four subjects among the survivors were not found. The age-standardized annual incidence rates of alcoholism ranged from 2·8 to 4·9% among the four aboriginal groups, and the rank order of rates was consistent with that of prevalences among these groups. The incidence rates of alcoholism were the highest among adolescents and young adults in men, and among the middle-aged in women.

Conclusions. High rates of first onset alcoholism among the Taiwanese aborigines indicate an interaction of sociocultural and biological factors in the development of such morbidity.

Background. A relationship between the anticonvulsant and antidepressant properties of electroconvulsive therapy (ECT) has been hypothesized. The goal of this study was to see whether the anticonvulsant effects of ECT could be measured in a clinical setting and whether there was any relationship between the anticonvulsant effects of ECT and the antidepressant response to it.

Methods. We examined the temporal relationship between change in seizure duration (as an index of anticonvulsant activity) and improvement in Hamilton Rating Scale for Depression scores in a retrospective sample of 114 depressed patients who received 145 courses of ECT. A linear mixed effects model was utilized for analysis so that the repeated measures nature of the data could be taken into account.

Results. Both seizure duration and depression scores decreased significantly through the course of ECT. However, no evidence was found for a relationship between decrease in seizure duration and clinical improvement as measured by Hamilton ratings.

Conclusions. The process underlying the reduction in seizure duration through a course of ECT may not be related to antidepressant efficacy.

Background. Genetic influences on alcoholism risk are well-documented in men, but uncertain in women. We tested for gender differences in genetic influences on, and risk-factors for, DSM-III-R alcohol dependence (AD).

Method. Diagnostic follow-up interviews were conducted in 1992–3 by telephone with twins from an Australian twin panel first surveyed in 1980–82 (N=5889 respondents). Data were analysed using logistic regression models.

Results. Significantly higher twin pair concordances were observed in MZ compared to DZ same-sex twin pairs in women and men, even when data were weighted to adjust for over-representation of well-educated respondents, and for selective attrition. AD risk was increased in younger birth cohorts, in Catholic males or women reporting no religious affiliation, in those reporting a history of conduct disorder or major depression and in those with high Neuroticism, Social Non-conformity, Toughmindedness, Novelty-Seeking or (in women only) Extraversion scores; and decreased in ‘Other Protestants’, weekly church attenders, and university-educated males. Controlling for these variables, however, did not remove the significant association with having an alcoholic MZ co-twin, implying that much of the genetic influence on AD risk remained unexplained. No significant gender difference in the genetic variance in AD was found (64% heritability, 95% confidence interval 32–73%).

Conclusions. Genetic risk-factors play as important a role in determining AD risk in women as in men. With the exception of certain sociocultural variables such as religious affiliation, the same personality, sociodemographic and axis I correlates of alcoholism risk are observed in women and men.

Background. The consequences of major depression for disability, impaired well-being and service utilization have been studied primarily in younger adults. In all age groups the consequences of minor depression are virtually unknown. In later life, the increased co-morbidity with physical illness may modify the consequences of depression, warranting special study of the elderly. With rising numbers of elderly people, excess service utilization by depressed elderly represents an increasingly important issue.

Methods. Based on a large, random community-based sample of older inhabitants of the Netherlands (55–85 years), the associations of major and minor depression with various indicators of disability, well-being and service utilization were assessed, controlling for potential confounding factors. Depression was diagnosed using a two-stage screening design. Diagnosis took place in all subjects with high depressive symptom levels and a random sample of those with low depressive symptom levels. The study sample consists of all participants to diagnostic interviews (N=646).

Results. As in younger adults, associations of both major and minor depression with disability and well-being remained significant after controlling for chronic disease and functional limitations. Adequate treatment is often not administered, even in subjects with major depression. As the vast majority of those depressed were recently seen by their general practitioners, treatment could have been provided in most cases. Bivariate analyses show that major and minor depression are associated with an excess use of non-mental health services, underscoring the importance of recognition. In multivariate analyses the evidence of excess service utilization was less compelling.

Conclusions. Both major and minor depression are consequential for well-being and disability, supporting efforts to improve the recognition and treatment in primary care. However, controlled trials are necessary to assess the impact this may have on service utilization.

Background. Smooth pursuit eye movement (SPEM) dysfunction is considered to be a promising candidate for a biological marker for genetic vulnerability to schizophrenia. There are conflicting findings regarding the question of what is exactly dysfunctional in SPEM dysfunction and what component of eye movements is really specific to schizophrenia. The purpose of the current study was to help to clarify the nature of (SPEM) dysfunction and its specificity to schizophrenia.

Methods. Smooth pursuit eye movements of 43 schizophrenic patients, 34 patients with major depression and 42 normal controls were examined using high resolution infrared oculography. These groups were compared on several indices of oculomotor functioning (gain, different saccadic categories).

Results. Schizophrenics had a significantly higher catch-up saccade rate than depressed patients and normals. The percentage of subjects with an abnormally high catch-up saccade rate defined as beyond the mean plus 2 s.d. of the normal control group was significantly higher in schizophrenics (27·9%) than in depressed patients (8·8%) and normal controls (0%). Low gain and higher numbers of intrusive saccades tended to be more prevalent in both patient groups but did not distinguish schizophrenics from depressed patients.

Conclusions. Low gain and high rates of intrusive saccades contribute to SPEM dysfunction in major depression. Abnormally high rates of catch-up saccades seem to be the oculomotor component in smooth pursuit, that is specific to schizophrenia.

Background. Although much research has focused on mechanisms of traumatization and factors related to post-trauma psychological functioning in survivors of trauma, there have been few studies of survivors of torture despite the widespread practice of torture in the world. The aim of this study was to examine the role of ‘psychological preparedness’ for trauma in post-traumatic stress responses in survivors of torture.

Method. Thirty-four torture survivors who had no history of political activity, commitment to a political cause or group, or expectations of arrest and torture were compared with 55 tortured political activists, using structured interviews and measures of anxiety, depression, and post-traumatic stress disorder.

Results. Compared with tortured political activists, tortured non-activists were subject to relatively less severe torture but showed higher levels of psychopathology. Less psychological preparedness related to greater perceived distress during torture and more severe psychological problems, explaining 4% of the variance in general psychopathology and 9% of the variance in post-traumatic stress disorder symptoms.

Conclusions. The study findings lend support to the role of prior immunization to traumatic stress and to unpredictability and uncontrollability of stressors in the effects of traumatization. Further research aimed at identifying the behavioural and cognitive components of psychological preparedness that play a role in traumatization may provide useful insights into effective treatment strategies for survivors of torture.

Background. It has been suggested that a failure to control for point in the menstrual cycle can lead to biased results in assessing psychiatric symptoms among women since state affects associated with premenstrual symptoms may lead to unreliability of symptom reporting as well as an artificial elevation of symptom ratings. We examine these hypotheses and the extent to which they can account for gender differences in symptom scale scores of demoralization and enervation.

Methods. The data are derived from an epidemiological study of Jews born in Israel between 1949 and 1958. The symptom scale scores of 2265 men and 1769 women (368 premenstrual, 458 menstruation and 943 postmenstrual) were compared regarding reliability, homogeneity and mean score.

Results. There were no differences among the menstrual groups, or between the men and women, in reliability of their responses as measured by the alpha coefficient and the coefficient of variation. There were no significant differences among the female groups on mean symptom scale score. The mean scale scores for each female group were significantly higher than the mean scores for men.

Conclusions. Our results suggest that menstrual cycle stage does not influence the reliability of reporting, the variability of response or mean symptom levels. However, our conclusions may not apply to studies of drug effects or clinical studies of premenstrual dysphoria.