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Current Psychiatry Reviews
ISSN: 1573-4 005
Current Psychiatry Reviews
Volume 2, Number 1, February 2006
Contents
Editorial Pp. 1
Issues in the Psychiatric Screening of Cancer Patients
Pp. 3-10
Colin R. Martin and Karis K.F. Cheng
[Abstract]
Neuropsychological Findings in Obsessive-Compulsive
Disorder and its Potential Implications for Treatment
Pp. 11-26
Leonardo F. Fontenelle, Mauro V. Mendlowicz, Paulo Mattos
and Márcio Versiani
[Abstract]
Transgenic Mouse Studies Reveal Substantial Roles
for Opioid Receptors in the Rewarding Effects of Several Classes
of Addictive Drugs Pp. 27-37
F. Scott Hall and George R. Uhl
[Abstract]
Proton Magnetic Resonance Spectroscopy as a Monitoring
Tool for Electroconvulsive Therapy Effects on the Brain
Pp. 39-49
Alexander Sartorius, Fritz A. Henn and Gabriele Ende
[Abstract]
Monoamine Receptors and Signal Transduction Mechanisms
in Suicide Pp. 51-75
Ghanshyam N. Pandey and Yogesh Dwivedi
[Abstract]
Pharmacogenetics of Cytochrome P450 (CYP) 1A2 and
Variability in Psychotropic Drug Response Pp. 77-94
Juan Antonio Carrillo and Guillermo Gervasini
[Abstract]
Women and Schizophrenia: Sex-Based Pharmacotherapy
Pp. 95-101
Judith Usall, Marta Barceló and Manel
Márquez
[Abstract]
Evidence that Cortical Dopamine is a Co-Transmitter
in Noradrenergic Neurons Pp. 103-109
Paola Devoto and Giovanna Flore
[Abstract]
Neuroimaging of the Serotonin Transporter: Possibilities
and Pitfalls Pp. 111-149
Peter Brust, Swen Hesse, Ulrich Müller
and Zsolt Szabo
[Abstract]
Postpartum Psychiatric Disorders: What Do We Know
and Where Do We Go? Pp. 151-158
Sophie Grigoriadis and Sarah Romans
[Abstract]
Adolescent Alcohol Abuse and Dependence: Development,
Diagnosis, Treatment and Outcomes Pp. 159-177
Dawn L. Thatcher and Duncan B. Clark
[Abstract]
Abstracts
[Back to top]
Editorial
I am delighted to assume the helm as Editor-in-Chief of
Current Psychiatry Reviews and would like to use this
editorial as both a brief introduction and to outline my vision
for CPSR. I have focused my career on academic psychiatry
for the assessment and treatment of mood disorders, both unipolar
and bipolar. For the past decade, my primary research activities
have been centered on various topics in therapeutics, including
research on older and newer antidepressants (Thase, Rush,
and Trivedi, 1995; Thase, Entsuah and Rudolph, 2001; Thase
et al., 2005), focused psychotherapies (Thase et
al., 1996; Thase et al., 1997a), and their combinations
(Thase et al., 1997b; Thase et al., 2002),
as well as the methodology of clinical trials (Thase, 1999;
Thase, 2002).
In early 2006, I will quietly celebrate the 30th anniversary
of publishing my first peer-reviewed paper (Thase and Moss,
1976). This small randomized clinical trial compared several
behavioral methods to treat simple phobia (excessive fear
of a nonpoisonous snake) in 30 college student volunteers.
Oh, how the content and process of clinical research has changed
across the intervening years! There have been mind-boggling
advances in neuroscience; research strategies that were in
their infancy in the mid-1970s, ranging from molecular genetics
to neuroimaging, have clearly come of age and now define the
“cutting edge” of research on the mechanisms of
vulnerability, pathophysiology, and therapeutic actions on
the major mental disorders. Had our little snake phobia study
been conceived in 2005, we might have studied how a behavioral
intervention leads to reallocation of cerebral blood flow
and energy consumption, examined the relationship between
genotypes and the persistence of fearfulness, or assessed
whether sustained reduction of fearfulness affects brain derived
neurotrophic factor levels. Better understanding of the impact
of various biases on research results also have emerged, as
well as more sophisticated approaches to statistical analyses.
In particular, three topics of great relevance to the readers
of CPSR come to mind: 1) the pernicious influence
of the “file drawer effect” – the selective
publication of positive reports and, conversely, the suppression
of negative ones – on reviews of the literature; 2)
the endemic problem created by Type II error, i.e., when inadequate
statistical power leads to the false conclusion that “not
statistically significantly different” actually means
that there is no difference; and 3) the impact that one’s
beliefs, allegiances, and affiliations can have on influencing
the results of both quantitative research and qualitative
reviews.
Given the proliferation of journals and the veritable explosion
of research results, now more than ever before there is great
need for concise, accessible and unbiased reviews that summarize
and – whenever possible – systematically synthesize
bodies of evidence. Hence, the mission and aims of CPSR:
to provide rapid publication of the most up-to-date reviews
of the latest advances in clinical psychiatry broadly defined.
Whereas our field’s most prestigious journals may publish
one or two review papers in each issue, each issue of CPSR
will include 10 or more such reviews, with sufficient breadth
of coverage to interest both generalists and ultrasubspecialists
alike. To help accomplish these goals, I am proud to say that
we have assembled a truly outstanding international Editorial
Advisory Board, which includes experts spanning all relevant
domains of research in psychiatry, including psychopharmacology,
psychotherapy, epidemiology, nosology, child psychiatry, geriatric
psychiatry, psychotherapy, forensics, and clinical and molecular
genetics. Please help me to keep this stellar Board busy with
a steady stream of manuscripts – I look forward to the
day in which our publisher, Bentham Science Publishers, Ltd.,
is obliged to make CPSR a monthly enterprise!
Michael E. Thase
(Editor-in-Chief)
University of Pittsburgh, School of Medicine
Western Psychiatric Institute and Clinic
Department of Psychiatry
3811 0 Hara Street
Pittsburgh, PA 15213-2593
USA
Tel: 412-246-5290
E-mail: thaseme@upmc.edu
[Back to top]
Issues in the Psychiatric Screening of Cancer Patients
Colin R. Martin and Karis K.F. Cheng
The experience of cancer represents a unique challenge to
both the physical and psychological health of the individual.
High levels of distress are common in cancer patients irrespective
of the type of pathology. However, the physiological aspects
of the disease process may be a source of confound in the
psychiatric screening process, thereby reducing the accuracy
of case identification. The current review examines the salient
factors which should be considered by clinicians when screening
for clinically significant psychological distress. The review
will evaluate the strengths and limitations of contemporary
screening instruments within this context and suggest approaches
to maximize screening accuracy in this clinical group. Finally,
the review will consider issues in the efficiency of the referral
pathway to liaison psychiatry services for those patients
positively screened. Implications for current psychiatric
practice and the direction of future research are also discussed.
[Back to top]
Neuropsychological Findings in Obsessive-Compulsive
Disorder and its Potential Implications for Treatment
Leonardo F. Fontenelle, Mauro V. Mendlowicz, Paulo Mattos
and Márcio Versiani
Neuropsychological studies have shed light on several important
aspects of obsessive-compulsive disorder (OCD). Along with
neuroimaging and information processing approaches, it has
contributed to delineate some of the most instigating pathophysiological
models of OCD and to strengthen its diagnostic validity. Lately,
neuropsychological studies have also emerged as a potentially
relevant research area for therapeutics. In this review, we
described the nature of the executive dysfunctions associated
with OCD and theorized how they may account for the characteristic
memory and visuoconstructive/visuospatial impairments found
in patients suffering from this disorder. We also examined
the concepts of implicit memory, meta-memory, memory for actions,
memory bias, reality monitoring, and the multiple ways these
functions may be altered in patients with OCD. The role of
cognitive dysfunctions as potential predictors of treatment
response to either pharmacological approaches (e.g. serotonin
reuptake inhibitors) or to cognitive-behavior therapies (i.e.
exposure and response prevention) in patients with OCD was
also discussed. Finally, we argued that cognition might be
an area of particular vulnerability to the negative effects
of the anti-obsessional drugs and of the neuroanatomically-based
approaches (neurosurgery and deep-brain stimulation).
[Back to top]
Transgenic Mouse Studies Reveal Substantial Roles
for Opioid Receptors in the Rewarding Effects of Several Classes
of Addictive Drugs
F. Scott Hall and George R. Uhl
In recent years transgenic studies in mice, in particular
those utilizing gene knockout techniques, have greatly contributed
to our understanding of the molecular mechanisms of drug reward
and drug abuse. Many of the initial gene knockouts that have
been created focused on the initial molecular targets of drugs
of abuse such as the μ
opiate receptor (MOR) for morphine, the dopamine transporter
(DAT) for cocaine and the vesicular monoamine transporter
2 (VMAT2) for amphetamine. These met with varying degrees
of success; for instance, although gene deletion of MOR eliminated
virtually all of the effects of morphine, the effects of cocaine
were eliminated only by combined deletion of DAT and the serotonin
transporter (SERT). However, such studies only address the
role of these genes in the actions of a single drug, and not
potential contributions to the rewarding and addictive properties
of drugs of abuse more generally. Studies of MOR KO mice have
been done for a number of addictive drugs and it has become
apparent that MOR KO affects the rewarding consequences of
a wide range of addictive substances. This contrasts quite
sharply with the consequences of other gene deletions, including
deletion of the other opiate receptor genes. Furthermore,
this conclusion suggests that variants in the MOR gene itself
or variation in MOR gene expression may influence susceptibility
to drug abuse and provide a common molecular target for treating
a wide range of addictions.
[Back to top]
Proton Magnetic Resonance Spectroscopy as a Monitoring
Tool for Electroconvulsive Therapy Effects on the Brain
Alexander Sartorius, Fritz A. Henn and Gabriele Ende
Electroconvulsive therapy (ECT) is still the most effective
treatment not only for psychotic depression, but also for
treatment of resistant or other severe forms of major depressive
episodes. Nevertheless, the exact nature of the therapeutic
effect of ECT is unknown. Modern theories of depression suggest
changes of synaptic plasticity especially within the hippocampus.
It was hypothesized that such changes may be reflected in
changes of proton magnetic resonance spectroscopy (1H
MRS) detectable signals.
The current literature on 1H MRS studies on ECT
effects is small with a large diversity of MRS methods applied,
brain regions studied and metabolite changes found. Nevertheless,
there is good evidence that changes in neurometabolite concentrations
are induced by ECT that can be non invasively monitored by
1H MRS. There also are pioneering 1H
MRS studies on animal models of depression: the Learned Helplessness
model in rats and the chronic social stress model in tree
shrews.
The proposed review will summarize the current MRS findings
in humans and animals and discuss possible interpretations.
[Back to top]
Monoamine Receptors and Signal Transduction Mechanisms
in Suicide
Ghanshyam N. Pandey and Yogesh Dwivedi
Suicide is a major public concern and in the teenage population
it is the third leading cause of death. Its neurobiology is
not well-understood, but recent postmortem brain studies have
provided greater understanding of the neurobiological abnormalities
associated with suicide. Earlier postmortem brain studies
focused on monoamine receptor subtypes, namely, serotonin,
e.g., (5HT)1A, 5HT2A, and adrenergic
receptors. Later, various components of the signaling cascades
to which these receptors are linked were examined; 5HT2A
or α1-adrenergic
receptors are linked to the phosphoinositide (PI) signaling
system, and β-adrenergic
receptors are linked to the adenylyl cyclase (AC) system.
These studies revealed abnormalities in the components of
the signaling systems: G proteins, the effectors phospholipase
C (PLC) and AC, or second and third messengers systems, such
as protein kinase C (PKC) and protein kinase A (PKA). Further
studies found that downstream transcription factors, such
as cAMP-response-element-binding protein (CREB), were also
affected. Here we critically review the studies, focusing
primarily on monoamine receptors and the components of PI
and AC signaling cascades in suicide, primarily in postmortem
brain. These studies provide a better understanding of the
pathophysiological abnormalities associated with suicide and
may lead to new therapeutic agents targeting specific sites
in the signaling cascade.
[Back to top]
Pharmacogenetics of Cytochrome P450 (CYP) 1A2 and
Variability in Psychotropic Drug Response
Juan Antonio Carrillo and Guillermo Gervasini
Despite the availability of a wide range of different drug
classes for the management of psychiatric disorders, the efficiency
of drug treatment is far from optimal. Regardless of the initial
choice and dose of standard psychiatric medication, about
30-50% of patients will not respond sufficiently to acute
treatment while others suffer from severe adverse drug reactions.
The patient-to-patient differences in drug response can be
explained on the basis of variability in drug pharmacokinetic
and pharmacodynamic processes. The involvement of the human
polycyclic aromatic hydrocarbon (PAH)-inducible CYP1A2 in
the metabolism of several psychotropic drugs is increasingly
acknowledged. Currently, it is well-known that this enzyme
shows a wide interindividual variability, but controversy
has long surrounded the issue of a polymorphic distribution
of the enzyme activity leading to pronounced differences in
drug response. Moreover, whether genetic polymorphism and/or
environmental factors play a definitive role has not yet unequivocally
established. On the other hand, combination pharmacotherapy
is commonly used in clinical psychiatry, and the CYP1A2 enzyme
is the target of many clinically relevant drug interactions.
This review is dealing with factors that could better explain
patient-to-patient differences in drug response to psychotropic
drugs, including CYP1A2 genetic polymorphisms, environmental
factors as well drug interactions modulating the CYP1A2 enzyme
activity.
[Back to top]
Women and Schizophrenia: Sex-Based Pharmacotherapy
Judith Usall, Marta Barceló and Manel
Márquez
Sex-based pharmacotherapy is a new research and clinical
area which could be characterized by the inclusion of sex-related
variables in clinical, research and educational issues with
respect to pharmacotherapy. In this article we will review
the studies that evaluate the treatment of schizophrenia with
respect to sex considerations.
First we will report the findings about sex differences in
response to treatment: pharmacokinetic sex differences and
differences in effectiveness of response to antipsychotics.
We will further review the studies that evaluate the use
of estrogens as an adjuvant treatment in women with schizophrenia:
in patients with premenstrual worsening of symptoms or in
resistant forms of the illness. Also, the possible use of
raloxifene (a selective estrogen receptor modulator) as an
adjuvant treatment in some postmenopausal schizophrenic women
will be discussed.
Finally we will review the endocrinal/sexual adverse effects
of antipsychotics in women.
[Back to top]
Evidence that Cortical Dopamine is a Co-Transmitter
in Noradrenergic Neurons
Paola Devoto and Giovanna Flore
Dopamine and noradrenaline in the prefrontal cortex modulate
superior cognitive functions and are implicated in the aetiology
of depressive and psychotic symptoms. Experimental evidence
reveals parallel variations in extracellular concentration
of both catecholamines in the cerebral cortex. In this review,
data are presented suggesting that extracellular dopamine
in the cerebral cortex originates not only from dopaminergic
terminals but also from noradrenergic ones, where it acts
both as precursor for noradrenaline and as co-transmitter.
Since the release of noradrenaline is controlled by alpha2-autoreceptors,
it follows that release and extracellular concentration of
both dopamine and noradrenaline in the cerebral cortex are
controlled by alpha2-autoreceptors and noradrenaline
transporter, whereas dopamine receptors and dopamine transporter
do not seem to be involved in these processes.
Atypical antipsychotics such as clozapine, and antidepressants
such as mirtazapine, increase noradrenaline and dopamine release
throughout the cerebral cortex, but not, or to a lesser extent,
in subcortical areas. On the other hand, D2 selective
drugs such as haloperidol, are potent in increasing dopamine
levels in subcortical dopaminergic areas but are ineffective
on dopamine and noradrenaline levels in the prefrontal cortex.
Local stimulation or inhibition of locus coeruleus neurons
by means of drug perfusion or electrical stimulation gives
rise to parallel variations of noradrenaline and dopamine
levels in the cerebral cortex, but not in prevalently dopaminergic
subcortical areas.
Extracellular dopamine of noradrenergic origin might represent
the major portion of total extracellular dopamine not only
in cortices with scarce dopaminergic innervation, such as
the parietal and occipital cortex, but also in the densely
innervated medial prefrontal cortex. In conclusion, drugs
acting on the co-release mechanism of noradrenaline and dopamine
may represent a tool with which to increase the selective
output of dopamine in the cerebral cortex.
[Back to top]
Neuroimaging of the Serotonin Transporter: Possibilities
and Pitfalls
Peter Brust, Swen Hesse, Ulrich Müller
and Zsolt Szabo
Nuclear medicine imaging techniques like positron emission
tomography (PET) and single-photon emission computed tomography
(SPECT) apply radiolabeled drugs that bind selectively to
specific neurotransmitter receptors and transporters such
as the serotonin transporter (SERT) in the living human brain.
They can help overcome certain limitations of postmortem,
platelet and genetic studies of the SERT. This review compares
the outcome of those studies with recent neuroimaging findings.
The first part of this review deals with the choice of radioligands
used to quantify SERT distribution in the human brain. The
second part summarizes studies performed to understand the
normal physiology of the serotonergic system. Selective serotonin
reuptake inhibitors (SSRIs), used to treat a wide range of
neuropsychiatric disorders with emotional instability and
behavioral control deficits, compete with SERT radioligands
and have been investigated in pharmacological PET and SPECT
studies in healthy volunteers and patients. Part three reviews
SERT imaging studies in patients, which have meanwhile been
performed in most disorders that benefit from SSRI treatment.
It is hypothesized that serotonin deficits and neuropsychiatric
symptoms are linked by the inhibition of involuntary emotional
reactions to external and internal stimuli. This could explain,
why the consistency of many SERT neuroimaging findings is
low, and may help develop individual treatment strategies
in therapy-nonresponsive cases and to engineer new drugs for
the therapy of neuropsychiatric disorders.
[Back to top]
Postpartum Psychiatric Disorders: What Do We Know
and Where Do We Go?
Sophie Grigoriadis and Sarah Romans
Biological, psychological as well as sociocultural changes
occur during the postpartum period and it is a high-risk time
for significant psychiatric illness. Postpartum psychiatric
disorders had been described for centuries yet these disorders
today are still poorly recognized and under-treated. They
are currently categorized into postpartum blues, postpartum
depression and postpartum psychosis. Panic disorder, Obsessive-Compulsive
Disorder, Generalized Anxiety Disorder and Posttraumatic Stress
Disorder typify the anxiety disorders of this period. This
mini-review describes what is known about postpartum psychiatric
disorders in terms of their clinical presentation, etiology
and treatment. Lactation issues, the impact on the child,
cultural considerations as well as life cycle challenges are
also discussed. Significant findings are critically reviewed
and potential future research directions that could lead to
substantial advancements are identified.
[Back to top]
Adolescent Alcohol Abuse and Dependence: Development,
Diagnosis, Treatment and Outcomes
Dawn L. Thatcher and Duncan B. Clark
Alcohol abuse and dependence are among the most common psychiatric
disorders occurring in adolescents. This article will examine
clinically relevant research on the development, diagnosis,
course, treatment, and adult outcomes of adolescent alcohol
use disorders (AUDs). A developmental history of childhood
mental disorders reflecting psychological dysregulation predicts
adolescent AUDs. The DSM-IV AUD definitions developed for
adults are generally valid for adolescents, although some
adolescents with significant alcohol problems are not identified
by this diagnostic system. Adolescents with AUDs typically
have other substance involvements, comorbid mental disorders,
and problematic family relationships. While biomedical complications
seen in chronic alcoholic adults are typically absent, acute
biomedical complications of intoxication, such as alcohol
poisoning or traumatic injury, may contribute to excess mortality
in adolescents. Psychosocial interventions promoting abstinence
are the most common treatments for AUDs, with credible empirical
support available for family-based approaches. While few drug
trials have been completed for adolescents with AUDs, pharmacological
interventions are available for alcohol withdrawal, craving,
and comorbid mental disorders. Some adolescents with AUDs
manifest chronic alcoholism in adulthood; many others transition
to abstinence or normative drinking. Alcohol abstinence is
the primary treatment focus, although other complications
need to be addressed and treated to foster optimal clinical
outcomes.
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