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Understanding the Pathology of Schizophrenia: The Impact of High-Throughput Screening of the Genome and Proteome in Postmortem CNS Pp.1-9
Brian Dean, Dahlia Keriakous, Elizabeth Thomas and Elizabeth Scarr
[Abstract] [Full text article]

Context Processing and Social Cognition in Schizophrenia Pp.11-22
Melissa J. Green, Peter J. Uhlhaas and Max Coltheart
[Abstract] [Full text article]

Toxic Psychoses as Pharmacological Models of Schizophrenia Pp.23-32
Potvin Stéphane, Stip Emmanuel and Roy Jean-Yves
[Abstract] [Full text article]

The Brain Epinephrine-α₁-Adrenoceptor System in Behavioral Activation and Depression Pp.33-43
Eric A. Stone and David Quartermain
[Abstract] [Full text article]

Recent Advances in the Pharmacotherapeutic Management of Drug Dependence and Addiction Pp.45-67
Christian Heidbreder
[Abstract] [Full text article]

What does the Hospital Anxiety and Depression Scale (HADS) Really Measure in Liaison Psychiatry Settings? Pp.69-73
Colin R. Martin
[Abstract] [Full text article]

Current Pathophysiological Findings in Bipolar Disorder and in its Subtypes Pp.75-101
Peter H. Silverstone, Brent M. McGrath, Phillip H. Wessels, Emily C. Bell and Michele Ulrich
[Abstract] [Full text article]

A Systematic Review of the Effectiveness of Oral Melatonin for Adults (18 to 65 Years) with Delayed Sleep Phase Syndrome and Adults (18 to 65 Years) with Primary Insomnia Pp.103-113
Kenneth M A MacMahon, Niall M Broomfield, Colin A Espie
[Abstract] [Full text article]

Abstracts

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Understanding the Pathology of Schizophrenia: The Impact of High-Throughput Screening of the Genome and Proteome in Postmortem CNS
Brian Dean, Dahlia Keriakous, Elizabeth Thomas and Elizabeth Scarr
[Full text article]

High-throughput screening technologies such as microarrays and 2D electrophoresis are powerful analytical tools particularly suited to investigating the pathologies of complex diseases. Schizophrenia is now widely recognised as a complex disorder resulting from the interplay between genetic predisposition to the illness and the effects of yet to be identified environmental factors. Based the hypothesis that the outcome of the interaction between genetic predisposition and environmental factors act to produce changes in protein expression in the CNS to cause schizophrenia, a number of studies have used postmortem CNS and highthroughput screening technologies to identify potential pathological processes that might be involved in the pathology of the disorder. This review attempts to place the current findings on gene and protein expression data in postmortem CNS from subjects with schizophrenia into a perspective that allows hypotheses on the cause of the disorder to be formulated.

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Context Processing and Social Cognition in Schizophrenia
Melissa J. Green, Peter J. Uhlhaas and Max Coltheart
[Full text article]

Recent empirical and theoretical work has conceptualized cognitive deficits in schizophrenia in terms of a deficit in the processing of contextual information [1, 2]. Context processing deficits have been shown to underlie impairments in multiple cognitive domains, and may thus represent a core disturbance in information processing in schizophrenia. Despite the increasing evidence for impaired context processing, there has been little research into the relevance of these deficits for an understanding of social cognition in schizophrenia. In the present paper, we argue that deficits in the processing of context may also be relevant for explanations of deficits in social cognition in schizophrenia. We review evidence to suggest that efficient context processing may be necessary for the acquisition and maintenance of social cognitive skills, such that deficits in context processing may be a common factor underlying deficits in both social and non-social cognition in schizophrenia. Future research should examine relationships between specific social cognitive skills (such as facial expression perception, mental state inference) in relation to context processing during non-social perceptual and cognitive tasks.

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Toxic Psychoses as Pharmacological Models of Schizophrenia
Potvin Stéphane, Stip Emmanuel and Roy Jean-Yves
[Full text article]

To simplify the understanding of schizophrenia, psychiatry has invested important efforts into the modelling of the disease. For obvious ethical reasons, sleep deprivation and sensory deprivation models have been rejected in the last decades. Thus, the psychotic disorders induced by psychoactive substances remain the main heuristic models of schizophrenia. Most of the work in the pharmacological modelling of schizophrenia has occurred in the sixties and seventies. Still, some observations retain their interest: 1) lasting up to six months, the amphetamine psychosis remains the best model of the positive symptoms of paranoid schizophrenia; 2) hallucinogens such as LSD or psilocybine reproduce, at best, the psychotic phenomenology observed during the first episodes of schizophrenia; 3) anesthetic dissociatives (PCP & ketamine) faithfully reproduce thought disorder, as well as the frontal cognitive deficits and certain negative symptoms of schizophrenia; 4) cannabis reproduces with fidelity the depersonalization states observed among schizophrenics; 5) alcohol hallucinosis could be the best model of the patients’ hallucinations; 6) the psychotic disorder induced by muscarinic antagonists is not usually considered as a schizophrenia model, but its occurrence signals that cholinergic dysfunctions could be associated with the cognitive symptoms of the disease. As such, these observations go hand in hand with the common view of schizophrenia as a pathology of general cerebral disconnectivity that would affect a plurality of neurotransmitter systems.

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The Brain Epinephrine-α₁-Adrenoceptor System in Behavioral Activation and Depression
Eric A. Stone and David Quartermain
[Full text article]

Disabling behavioral inactivity is a prominent symptom of a number of psychiatric disorders, most notably, major depressive illness. The neurobiology of these inactive states is currently believed to involve alterations in central serotonergic, noradrenergic or dopaminergic neurotransmission as affected by various etiological and predisposing factors. Recent evidence suggests that there is another system that consists of a subset of brain α₁-adrenoceptors stimulated primarily by brain epinephrine (EPI) that potentially modulates the above three monoamine systems and plays a critical role in behavioral activation and depression. The present review covers the evidence for this system and includes findings that brain α₁-adrenoceptors are instrumental in behavioral activation, are located near the major monoamine cell groups or target areas, receive EPI as their neurotransmitter, are impaired or inhibited in depressed patients or after stress in animal models, and are restored by a number of antidepressants. This “EPI-α₁ system” may therefore represent a new target system for disabling inactivity.

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Recent Advances in the Pharmacotherapeutic Management of Drug Dependence and Addiction
Christian Heidbreder
[Full text article]

Drug addiction is a syndrome of impaired response inhibition and salience attribution, which involves a complex neurocircuitry underlying drug reinforcement, drug craving and compulsive drugseeking and -taking behaviours despite adverse consequences. The continued elucidation of the neurobiological underpinnings of withdrawal symptoms, drug intake, craving, relapse, and co-morbid psychiatric associations has significantly boosted the development of new pharmacotherapies for the treatment of drug addiction. The present review will focus on recent advances in the development of innovative pharmacotherapeutic agents, which should promote long-lasting drug abstinence and longterm recovery, ensure satisfactory patient compliance, and have a good safety profile.

First, the magnitude of the drug dependence problem will be presented by reviewing some of the most recent epidemiological data. Second, a short overview of the neurobiological substrates of drug craving and addiction will be presented. We will show that despite individual variation in the liability to the abuse of psychoactive substances, there is substantial commonality shared by drugs of abuse. The knowledge of these common mechanisms is critically important for the development of new therapeutic strategies. Third, pharmacological approaches and drug development strategies will be thoroughly discussed. The most promising strategies will be presented by reviewing key targets for drug discovery at both clinical and pre-clinical levels.

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What does the Hospital Anxiety and Depression Scale (HADS) Really Measure in Liaison Psychiatry Settings?
Colin R. Martin
[Full text article]

The hospital anxiety and depression scale (HADS) is a widely used and popular self-report measure that has been extensively translated and utilized in a broad variety of clinical populations. This 14-item measure has been subject to two previous reviews exploring a number of psychometric aspects of this tool. A relatively consistent finding of previous reviews of this instrument is that it is a reliable and valid measure of two independent and separable dimensions of anxiety and depression; indeed, this aspect of the HADS is crucial to the validity of the measure in clinical practice. The current review examines contemporary research reports that use factor analytic techniques, which suggest that the assumed bi-dimensionality of the HADS is, in fact, erroneous. The findings from the current review suggest that the HADS is underpinned by a tridimensional factor structure comprising dimensions of anhedonia, negative affectivity and autonomic arousal. Implications for the use of the HADS in light of these observations are discussed and recommendations made within the context of screening practice for the referral to liaison psychiatry services.

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Current Pathophysiological Findings in Bipolar Disorder and in its Subtypes
Peter H. Silverstone, Brent M. McGrath, Phillip H. Wessels, Emily C. Bell and Michele Ulrich
[Full text article]

There have been many studies that have examined various aspects of the pathophysiology of bipolar disorder, with many positive findings in several areas of neuroimaging and metabolic abnormality. These studies might allow some conclusions to be drawn about the underlying pathophysiology. Additionally, it is of significant interest to determine if there are pathophysiological differences between patients with bipolar disorder type I (BPD-I) and those with bipolar disorder type II (BPD-II). The present review examines imaging studies in bipolar patients of possible structural changes (magnetic resonance imaging (MRI)) functional changes (focusing on functional MRI (fMRI), positron emission tomography (PET), and single photon emission computed tomography (SPECT)), and those examining brain chemistry (utilizing magnetic resonance spectroscopy (MRS)). Metabolic studies reviewed were those that examined 3-methoxy-4- hydroxyphenylglycol (MHPG), cellular calcium, and protein kinase C (PKC). The results clearly suggest that BPD patients differ from controls on many of these measures. However, while there is evidence from genetic studies suggesting possible differences between BPD-II patients and BPD-I patients, the neuroimaging and metabolic studies to date do not support this, and there appear to be no consistent pathophysiological differences between these subtypes from evidence available at present.

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A Systematic Review of the Effectiveness of Oral Melatonin for Adults (18 to 65 Years) with Delayed Sleep Phase Syndrome and Adults (18 to 65 Years) with Primary Insomnia
Kenneth M A MacMahon, Niall M Broomfield, Colin A Espie
[Full text article]

Oral melatonin supplementation has been heralded as a treatment for the sleep disorders of delayed sleep phase syndrome (DSPS) and primary insomnia (PI) in adults (18 to 65 years). However, there is inconsistency in the literature and many of the claims for melatonin appear to be based upon its effect in older adults (> 65 years). This article reviews, systematically, studies of oral melatonin in adults (18 to 65 years) with either delayed sleep phase syndrome (DSPS) or primary insomnia (PI).

Following electronic database searching, and hand-searching of relevant journal titles, fourteen articles that examined the use of melatonin in adults with PI or DSPS were identified for inclusion in this review (eight for DSPS and four for PI). Generally, the quality of articles is limited, particularly with regard to reporting of sleep parameters. However, results indicate that melatonin may phase-advance the sleep of individuals diagnosed with DSPS, although the majority of this evidence comes from uncontrolled trials. There is little evidence to suggest that melatonin is an effective treatment for PI. Further research, addressing deficiencies in the current literature, and considering long-term efficacy and safety are necessary before definitive conclusions as to the value of oral melatonin can be drawn.