Diagnostic trajectory, interplay and convergence/divergence across all 12 DSM-IV psychotic diagnoses: 6-year follow-up of the Cavan-Monaghan First Episode Psychosis Study (CAMFEPS).

BACKGROUND: The boundaries of psychotic illness and the extent to which operational diagnostic categories are distinct in the long term remain poorly understood. Clarification of these issues requires prospective evaluation of diagnostic trajectory, interplay and convergence/divergence across psychotic illness, without a priori diagnostic or other restrictions. METHOD: The Cavan-Monaghan First Episode Psychosis Study (CAMFEPS), conducted using methods to attain the closest approximation to epidemiological completeness, incepts all 12 DSM-IV psychotic diagnoses. In this study we applied methodologies to achieve diagnostic reassessments on follow-up, at a mean of 6.4 years after first presentation, for 196 (97%) of the first 202 cases, with quantification of prospective and retrospective consistency. RESULTS: Over 6 years, the 12 initial psychotic diagnoses were characterized by numerous transitions but only limited convergence towards a smaller number of more stable diagnostic nodes. In particular, for initial brief psychotic disorder (BrP), in 85% of cases this was the harbinger of long-term evolution to serious psychotic illness of diagnostic diversity; for initial major depressive disorder with psychotic features (MDDP), in 18% of cases this was associated with mortality of diverse causality; and for initial psychotic disorder not otherwise specified (PNOS), 31% of cases continued to defy DSM-IV criteria. CONCLUSIONS: CAMFEPS methodology revealed, on an individual case basis, a diversity of stabilities in, and transitions between, all 12 DSM-IV psychotic diagnoses over 6 years; thus, psychotic illness showed longitudinal disrespect to current nosology and may be better accommodated by a dimensional model. In particular, a first episode of BrP or MDDP may benefit from more vigorous, sustained interventions.

The origin and course of schizophrenia: implications for clinical practice.

The authors first review current evidence concerning abnormalities of brain structure and function in schizophrenia and interpret them within a "network" pathophysiological model of the disorder. This information is then placed within a contemporary neurodevelopmental framework that "roots" the illness in adverse events during early pregnancy, which result in a developmentally compromised nervous system. They then consider the controversy as to whether the subsequent expression of psychosis reflects an active morbid process and, in a more general sense, whether the disorder is characterized by subsequent progression and clinical deterioration. The authors argue that the developmental and progressive models should not be considered in an either-or manner, since this perspective is not logical and favors nihilistic approaches to intervention and treatment, but rather should be integrated within a lifetime trajectory model. Finally, implications for current psychiatric practice are considered.

Epidemiology and pathobiology of bipolar disorder, and their exploration within a complete catchment area population.

Epidemiological and pathobiological findings in bipolar disorder [BP] have often been limited by selection bias and lack of epidemiological representativeness. In a rural, circumscribed catchment area, 'all' patients with BP were identified and assessed. On preliminary analysis, morbid risk [MR] for BP over the area as a whole was 5.0 ± 0.6/1000. The distribution of MR for BP over geographical subregions showed no significant deviation from a statistical model for random occurrences in space by place at birth, in contrast to schizophrenia [SZ], and varied only modestly among males by place at onset. These results imply different etiological factors acting in BP in comparison with SZ, particularly with regard to the role of early versus later life events. In preliminary analyses of psychotic and cognitive features, current severity of positive symptoms was predicted in BP only by increasing dominance of the left hand; negative symptoms by duration of illness and current anticholinergic exposure; poorer general and frontal cognitive function by older age at onset of illness, increasing duration of illness, and current anticholinergic exposure. The finding on handedness suggests disturbance of cerebral asymmetry associated with positive symptoms in BP, while both negative symptoms and cognitive impairment may involve progressive processes. Further analysis of this epidemiologically complete population, including systematic comparisons of BP with schizoaffective disorder and SZ, continues.

Geographical variation in rate of schizophrenia in rural Ireland by place at birth vs place at onset.

This study examined geographical variation in rate of occurrence of schizophrenia by place at birth vs place at onset, among a rural Irish catchment area population of unusual stability and socioeconomic homogeneity. Within a catchment area of 21,520 persons, all cases of schizophrenia were sought using current inpatient and outpatient records and key informants active in the community. Suspected cases were interviewed personally and diagnosed using DSM-III-R criteria. Place at birth and place at onset of psychosis were specified among the 32 District Electoral Divisions constituting the study region. For the 72 cases ascertained, an unremarkable overall prevalence rate/morbid risk obscured substantial and significant geographical variations therein between District Electoral Divisions. Particularly after controlling for high-density families, men demonstrated prominent geographical variation both by place at birth and by place at onset, with most men remaining unmarried and becoming ill at their place of birth; conversely, women demonstrated prominent variation by place at birth but more limited variation by place at onset, despite more frequent transitions from the parental home to the marital home before onset. Even when cases changed their location before the onset of psychosis, geographical variation in rate of occurrence of schizophrenia remained associated more strongly with factors related to the place of their birth.

Course of psychopathology, cognition and neurobiological abnormality in schizophrenia: developmental origins and amelioration by antipsychotics?

It is argued that schizophrenia has origins in events occurring during the first or early second trimester that are reflected in minor physical anomalies and which may at least in part predispose to later obstetric complications. This neurodevelopmental basis underlies certain neuromotor and psychosocial abnormalities of infancy and childhood, which are the early manifestations of what will be reconceptualised later as negative symptoms and (particularly frontal) cognitive dysfunction, but gives rise to positive symptoms only on the maturation of other systems necessary for their expression. This later emergence of psychosis may reflect an active morbid process that is associated with increased accrual of negative symptoms and of general (but not frontal) cognitive impairment that may be ameliorated by effective antipsychotic treatment. The psychological or biological basis of this heuristic process is poorly understood. Contemporary re-appraisal of any impact of antipsychotics on the long-term course of schizophrenia must take into account what is known of the origins of the disease process with which such drugs might interact. Much recent work continues to indicate that very early events, during the embryonic/fetal period, are important in, if not fundamental to, the genesis of schizophrenia; i.e. that there is a neurodevelopmental basis to the disorder. The present article seeks to establish a time-line relating early intrauterine adversity and dysmorphogenesis, through the onset of psychosis, to the chronic phase of the illness over adulthood; from this time-line, a schema is elaborated for a beneficial impact of antipsychotics on the course of psychopathology, cognition and, less clearly, neurobiological abnormality.

Neurodevelopmental and neuroprogressive processes in schizophrenia. Antithetical or complementary, over a lifetime trajectory of disease?

The neurodevelopmental model of schizophrenia maintains ascendancy among current etiopathologic perspectives on schizophrenia. However, inconsistencies across studies and the absence thus far of pathognomic brain changes suggest the need for complex conceptualization of neurodevelopmental arrest, including some reconciliation with the competing neurodegenerative model of schizophrenia. This article critically reviews the preponderance of evidence for each model and provides an account of how these may interact or synergize to produce the characteristic clinical expression of schizophrenia.

Psychopathology, executive (frontal) and general cognitive impairment in relation to duration of initially untreated versus subsequently treated psychosis in chronic schizophrenia.

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.

Executive (frontal) dysfunction and negative symptoms in schizophrenia: apparent gender differences in 'static' v. 'progressive' profiles.

BACKGROUND: While executive (frontal lobe) dysfunction appears to be a core feature of schizophrenia, its relationship to psychopathology, age and duration of illness has yet to be explored systematically between the genders. METHOD: Executive dysfunction, positive and negative symptoms were evaluated in 27 male and 21 female in-patients who were unusually well-matched on numerous demographic and clinical measures. RESULTS: Measures of executive dyscontrol and negative symptoms were highly associated in both genders. However, while both executive dyscontrol and negative symptoms increased prominently with age/ duration of illness among women, no such relationship was evident among men. CONCLUSIONS: The similarly prominent levels of current executive dyscontrol and negative symptoms in male and female patients appear to have emerged via processes that differ fundamentally between the genders; among males these deficits appear to emerge and become 'locked in' earlier in the course of illness and to show little subsequent increase, while among females these same deficits appear to be less evident early in the course but to increase in prominence thereafter.

Developmental trajectory and disease progression in schizophrenia: the conundrum, and insights from a 12-year prospective study in the Monaghan 101.

Though conceptualised originally as a deteriorating disorder, some contemporary studies have been interpreted as challenging these foundations; more radically, it has been proposed that schizophrenia may be a 'static encephalopathy' of neurodevelopmental origin. The argument offered here is that schizophrenia is indeed a neurodevelopmental disorder, but that this is not in itself antithetical to later disease progression. Rather, the onset of psychosis may reflect the maturationally-mediated triggering of an active disease process that is associated with progressive deterioration unless attenuated by antipsychotic drugs. A developmental trajectory is proposed to link first or early second trimester dysplasia to the chronic course of the illness; from this, it is argued that schizophrenia is inherently a progressive disorder but that antipsychotic drugs may act to ameliorate this progressive component and thus confer on the disease course some of the characteristics of a 'static encephalopathy'. The 'true' natural history of an illness cannot be determined from studies in treated populations.

The new antipsychotics, and their potential for early intervention in schizophrenia.

Over almost four decades, few fundamentally different antipsychotic drugs evolved to challenge classical neuroleptics as the mainstay of the pharmacotherapy of schizophrenia. However, the recent re-emergence of clozapine, together with the emergence of risperidone, portends an increasing number of new antipsychotics which are now either traversing the stages of regulatory approval or else well-advanced in clinical development. This article first evaluates the significance of clozapine and risperidone; it then reviews some of the new antipsychotics and how they might be classified vis-a-vis potential advantages for patients, outlines putative mechanisms and new therapeutic targets, and considers whether such agents may act on any disease process inherent to schizophrenia. One fundamental issue is the extent to which the new antipsychotics might shift materially the risk benefit balance towards intervention, not just at the earliest possible stage following the onset of psychosis but at a yet earlier, 'prodromal' phase of the disorder where there is a considerably greater likelihood of 'treating' behavioural disturbances that prove not to be the harbingers of psychotic illness.

Optical fibre-based goniometer for sensing patient position and movement within a magnetic resonance scanner using chromatic modulation.

An optical fibre-based goniometer is described. This instrument was designed to measure the angular position of patients' limbs within the core of a magnetic resonance body scanner, via a 40 m remote fibre-optic link. The sensor exploits the advantages of optical fibre-based sensing, which include immunity to electromagnetic interference, intrinsic safety and chemical immunity. The detection electronics and signal processing are based on the principles of chromatic modulation, an inexpensive, intensity-independent technique in which a change in the spectral power distribution is measured over a broad bandwidth, by photodetectors with differing spectral responses. The optical fibre goniometer has an angular range of 90 degrees, with an average resolution of 2'. The long-term accuracy is within +/- 1 degree, the specified accuracy for the physiological application.