The book review, from the Canadian Journal of Psychiatry, states:

Juvenile-Onset Schizophrenia: Assessment, Neurobiology and Treatment Robert L Findling, S Charles Schulz, editors. Baltimore (MD): Johns Hopkins University Press; 311 p. US$49.95.

The title of this book echoes the more familiar diagnosis of juvenile-onset diabetes and thus implies an illness different in cause and in course from one that begins in later adult years-an interesting speculation that is unfortunately not addressed in this book.

The first chapter discusses the phenomenology of adolescent-onset psychosis, which immediately introduces the core question: What is psychosis? As Gabrielle Carlson and others, the authors of Chapter 1, point out, the definition is “by no means fixed.” It is generally acknowledged that a relation exists between the various definitions of psychosis and the illness schizophrenia, but psychosis occurs in many other illnesses, and schizophrenia, by definition a psychotic illness, can at times be diagnosed without the usual signs of psychosis (that is, delusions and hallucinations). Nonetheless, the authors conclude that, whatever the diagnosis, psychosis in adoelscence is preceded by poor cognitive functioning and childhood psychiatric symptoms that need attending to as much, if not more, than the psychosis—a clinically relevant recommendation.

Chapter 2 zeroes in on schizophrenia and attempts a unitary and integrative glutaminergic developmental hypothesis to account for the known facts about this elusive illness. From a clinical point of view, this suggests that drugs that reduce glutamate release, such as lamotrigine, would be useful for treating schizophrenia. Lamotrigine has proven highly successful in the treatment of mood disorder, which again brings up the questions raised in Chapter 1: What is included in the term psychosis? In what way is schizophrenia a stand-alone illness?

Chapter 3, by Tonya White and Charles Nelson, is an informative review of neurobiological development during childhood and adolescence. Logically, however, it should have come at the beginning of the book.

Suicides peak in May and June in the Northern Hemisphere and in November and December in the Southern Hemisphere. Indeed, the risk increases between 8 and 50 percent in each of the 20 countries surveyed by Dimitrios Trichopoulos, M.D., a professor of epidemiology at the Harvard School of Public Health. “My suspicion is that sunlight affects suicide risk through hormonal factors like melatonin,” says Trichopoulos. Melatonin is suppressed by sunlight and is known to play a role in mood regulation. The hormones cortisol, serotonin and tryptophan may be affected by sunlight, as well.

There is also a seasonal pattern in the births of schizophrenics. Studies confirm a 10 percent increase in these births in the Northern Hemisphere between February and April. This trend, coupled with findings that children of dark-skinned immigrants to northern countries have high rates of schizophrenia, led scientists to surmise a shortage of sunlight as a possible factor in the illness.

Ultraviolet rays help the body manufacture vitamin D, and low prenatal levels of this vitamin alter key genes and nerve growth in rats’ brains. These disruptions are also found in the brains of schizophrenics, according to John McGrath, Ph.D., director of the Queensland Centre for Schizophrenia Research in Brisbane, Australia. McGrath, who has been studying vitamin D for four years, presented his most recent findings to the International Society for Developmental Neuroscience.

McGrath’s work was initially called eccentric, but it meshed perfectly with migrant studies indicating high rates of schizophrenia among second-generation immigrants. It takes dark-skinned people longer to produce vitamin D, so they are at a disadvantage when deprived of sunlight. “When I saw how common low vitamin D was in dark-skinned migrants to cold climates, it seemed to be a ‘theory of everything,’” says McGrath.

In experiments at Duke University Medical Center, nicotine patches boosted schizophrenics’ performance on tests of short-term memory and of mental processing speed abilities with which Haloperidol, the leading antipsychotic drug, interferes. Nicotine also improved participants’ attention spans as they tackled a boring computer task for 14 mind-numbing minutes, reports Duke professor of psychiatry Edward D. Levin, Ph.D., in the journal Neuropsycho-pharmacology.

However, given tobacco’s well-documented health hazards, Levin and his colleagues don’t recommend that schizophrenics cultivate a cigarette habit. But he says the study supports the idea that for schizophrenics, smoking is probably an unconscious attempt to restore some of their blunted mental abilities.

The finding hinges on measurements of some brain waves that arise from synchronized activity in large clusters of neurons.

In healthy adults listening to two different tones in a sequence, for example, these aligned brain waves occur about one-tenth of a second after a person first recognizes the tones’ difference, say neuroscientist Leanne M. Williams of Westmead (Australia) Hospital and her colleagues. The synchronized electrical outbursts appear most prominently in the frontal brain, a region regarded as a key part of a network that interprets novel perceptions against a background of prior knowledge.

In contrast, people diagnosed with their first bout of schizophrenia display a decline in neural synchrony, especially in the frontal brain, in the fraction of a second after discerning a particular tone, Williams’ team reports in the March American Journal of Psychiatry. Individuals with schizophrenia exhibit unusually low levels of synchronized neural firing to begin with, the researchers note.

If confirmed in further work, these findings raise the likelihood that “a breakdown in the synchrony of distributed neural networks is a marker for the onset of schizophrenia,” the researchers conclude.

The normal mice learned that in the first environment, the chocolate was linked to the first scent. When the researchers changed to a second environment, the mice learned to find the chocolate using the second scent.

Once the mice were trained, an area of the brain called the hippocampus was injected with a genetically engineered virus that selectively cut out the NR1 gene. NR1 produces a protein that is critical for molding nerve messages in an area of the hippocampus called the CA3, which is associated with distinguishing complex patterns. It is this molding that underlies the hippocampal-dependent learning and memory that is needed to distinguish the complex patterns.

The researchers then attempted to train the mice in memory tasks with new scents and new environments, but the animals lacking the gene couldn’t learn. The control group, which received an injection that doesn’t cut out NR1, learned as quickly as before.

This shows that the treated animals couldn’t react properly to situational cues, which also happens in people with schizophrenia, Dr. Greene said.

The researchers hope to see in future studies if similar small changes to nearby brain regions involved in learning and memory result in the same kind of problems.

“In addition, we want to use a similar task in humans to that used in this study to see if patients with schizophrenia have similar deficits in cognition as we observed in our experimental mice,” Dr. Greene said. “This will help determine whether our genetically altered animals provide a good model of the psychosis associated with schizophrenia.”

Former UT Southwestern researchers involved in the study were Dr. Tarek Rajji, a psychiatry resident now at the University of Pittsburgh, and Dr. David Chapman, a postdoctoral fellow now at UCB Pharma. Dr. Howard Eichenbaum of Boston University also participated in the study.