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The fluorescence in situ hybridization (FISH) is one of the fluorescence methods used for clinical testing and studying genes associated with childhood neuropsychiatric disorders. It has become an important tool in positional cloning strategies by linking the clinical data on patients with characteristic cytogenetic abnormalities and the information on the physical structure of the human genome from the human genome project. The simultaneous use of several spectrally distinct fluorophores is another major advantage of FISH.

One of the major problems undermining the effectiveness of linkage analysis for studying genetic disorders is the methods dependency on several parameters that are not known for most psychiatric disorders. Several nonparametric methods that do not rely on a priori determination of genetic parameters have been developed to address the problem. The two main types of nonparametric approaches are association and allele-sharing. The advantages and limitations of these approaches are discussed.

Gonadal steroid hormones may be the key to understanding sexual dimorphism in humans and animals. Studies show that these hormones participate in developing sexually dimorphic neural circuits in the spinal nucleus of the bulbocavernosus (SNB). These also affect genetic transcription toward the formation of sexual characteristics. This mechanism is best understood in the neural and behavioral control of birdsong. A study on the similarities between the sexual differentiation of vocal control circuits in zebra finches and the SNB can further expand the knowledge on sexual dimorphism.

Recent studies show that growth factors strongly influence the activity-dependent modification of the neuronal structure. Growth factors are also involved in the survival of neurons and in the growth of axons. Similar studies suggest that these same growth factors also play a role in the growth of dendrites in the visual cortex. Likewise, these growth factors improve synapses following their activation.

Programmed cell death, also called apoptosis, plays a critical role in the development of the cerebral cortex. Widespread cell death occurs during periods of cell genesis and the development of synaptic connections. Research has shown that apoptosis eliminates more than half of the neurons and glial cells during development of the central nervous system and that extensive cell death occurs in the proliferative zones of the developing cerebral cortex. Knowledge about the mechanisms behind programmed cell death is expected to have significant clinical benefits.

We recently demonstrated that a tonic activation of adenosine A2A receptors (A2ARs) is required for cocaine‐induced synaptic depression and increase in the activity of STriatal‐Enriched protein tyrosine Phosphatase (STEP). In this study, we elaborated on the relationship between A2AR and STEP using genetic, pharmacological, and cellular tools. We found that the activities of protein tyrosine phosphatases (PTPs), and in particular of STEP, are significantly increased in the striatum and hippocampus of a transgenic rat strain over‐expressing the neuronal A2AR (NSEA2A) with respect to wild‐type (WT) rats. Moreover the selective A2AR agonist 4‐[2‐[[6‐Amino‐9‐(N‐ethyl‐β‐d‐ribofuranuronamidosyl)‐9H‐purin‐2‐yl]amino]ethyl]benzenepropanoic acid hydrochloride up‐regulates PTPs and STEP activities in WT but not in NSEA2A rats, while the selective A2AR antagonist 4‐(−2‐[7‐amino‐2‐{2‐furyl}{1,2,4}triazolo{2,3‐a} {1,3,5}triazin‐5‐yl‐amino]ethyl)phenol restores the tyrosine phosphatase activities in NSEA2A, having no effects in WT rats. In addition, while cocaine induced the activation of PTP and STEP in WT rats, it failed to increase phosphatase activity in NSEA2A rats. A2ARs modulate STEP activity also in the SH‐SY5Y neuroblastoma cell line, where a calcium‐dependent calcineurin/PP1 pathway was found to play a major role. In summary, the present study identified a novel interaction between A2AR and STEP that could have important clinical implications, since STEP has emerged as key regulator of signaling pathways involved in neurodegenerative and neuropsychiatric diseases and A2ARs are considered a promising target for the development of therapeutic strategies for different diseases of the central nervous system. Read the Editorial Highlight for this article on page 270 [ABSTRACT FROM AUTHOR]

Describes the process by which a department of psychiatry computerized its clinical services under a single communication network. Presents the program in detail, demonstrating the recording of various clinical, administrative and demographic data. Emphasizes the value of such information for returning patients, immediate updating of information, and expanding the department's research capability. (Author/KS)

The effects of heat on tic symptoms were studied in a sample of 78 adults with Tourette syndrome. 62 men and 16 women completed a survey concerning the type, onset, and course of their tics. 10 adult male subjects also participated in a thermal challenge during which ambient temperature was raised from 22 [degrees] C to 35 [degrees] C following a control period. Of the 78, 24% or 19 reported increased tics upon exposure to heat. Compared to the remaining 59 subjects, there were no differences in sex distribution, current age, or overall course of illness. In the thermal challenge, there was general increase in tics that was correlated with sweat rate (r = .55, p = .001). This effect was prominent in 5 of 10 subjects (rs = .29 to .63). There were no mean differences in current age, age of onset, or current severity of symptoms between the five subjects of each group. Tic symptoms in a subgroup of patients with Tourette syndrome may be sensitive to heat. Abnormal heat regulation is not a likely explanation for the observed increase in tics. The increase may be due to normal heat-loss mechanisms through dopaminergic pathways.

The genetics of Huntington disease (HD) is discussed. Topics include the mutation associated with HD, the protein huntingtin, function of the normal protein, effect of the mutant protein, nuclear inclusions, and mouse models. A list of relevant Web sites is also provided.

The striatal-enriched protein tyrosine phosphatase (STEP) is a brain-specific phosphatase involved in synaptic transmission. The current hypothesis on STEP function holds that it opposes synaptic strengthening by dephosphorylating and inactivating key neuronal proteins involved in synaptic plasticity and intracellular signaling, such as the MAP kinases ERK1/2 and p38, as well as the tyrosine kinase Fyn. Although STEP has a predominant role at the post-synaptic level, it is also expressed in nerve terminals. To better investigate its physiological role at the presynaptic level, we functionally investigated brain synaptosomes and autaptic hippocampal neurons from STEP knockout (KO) mice. Synaptosomes purified from mutant mice were characterized by an increased basal and evoked glutamate release compared with wild-type animals. Under resting conditions, STEP KO synaptosomes displayed increased cytosolic Ca2+ levels accompanied by an enhanced basal activity of Ca2+/calmodulin-dependent protein kinase type II (CaMKII) and hyperphosphorylation of synapsin I at CaMKII sites. Moreover, STEP KO hippocampal neurons exhibit an increase of excitatory synaptic strength attributable to an increased size of the readily releasable pool of synaptic vesicles. These results provide new evidence that STEP plays an important role at nerve terminals in the regulation of Ca2+ homeostasis and neurotransmitter release. [ABSTRACT FROM AUTHOR]

NMDA receptor signaling is critical for the development of synaptic plasticity, learning, and memory, and dysregulation of NMDAR signaling is implicated in a number of neurological disorders including schizophrenia (SZ). Previous work has demonstrated that the STriatal-Enriched protein tyrosine Phosphatase 61 kDa (STEP61) is elevated in human SZ postmortem cortical samples and after administration of psychotomimetics to cultures or mice. Here, we report that activation of synaptic NMDAR by bicuculline or D-serine results in the ubiquitination and proteasomal degradation of STEP61, and increased surface localization of GluN1/GluN2B receptors. Moreover, bicuculline or D-serine treatments rescue the motor and cognitive deficits in MK-801-treated mice and reduce STEP61 in mouse frontal cortex. These results suggest that STEP61 may contribute to the therapeutic effects of D-serine. [ABSTRACT FROM AUTHOR]

Cocaine self-administration in rats results in dysfunctional neuroadaptations in the prelimbic (PrL) cortex during early abstinence. Central to these adaptations is decreased phospho-extracellular signal-regulated kinase (p-ERK), which plays a key role in cocaine seeking. Normalizing ERK phosphorylation in the PrL cortex immediately after cocaine self-administration decreases subsequent cocaine seeking. The disturbance in ERK phosphorylation is accompanied by decreased phosphorylation of striatal-enriched protein tyrosine phosphatase (STEP), indicating increased STEP activity. STEP is a well-recognized ERK phosphatase but whether STEP activation during early abstinence mediates the decrease in p-ERK and is involved in relapse is unknown. Here, we show that a single intra-PrL cortical microinfusion of the selective STEP inhibitor, TC-2153, immediately after self-administration suppressed post-abstinence context-induced relapse under extinction conditions and cue-induced reinstatement, but not cocaine prime-induced drug seeking or sucrose seeking. Moreover, an intra-PrL cortical TC-2153 microinfusion immediately after self-administration prevented the cocaine-induced decrease in p-ERK within the PrL cortex during early abstinence. Interestingly, a systemic TC-2153 injection at the same timepoint failed to suppress post-abstinence context-induced relapse or cue-induced reinstatement, but did suppress cocaine prime-induced reinstatement. These data indicate that the STEP-induced ERK dephosphorylation in the PrL cortex during early abstinence is a critical neuroadaptation that promotes relapse to cocaine seeking and that systemic versus intra-PrL cortical inhibition of STEP during early abstinence differentially suppresses cocaine seeking. [ABSTRACT FROM AUTHOR]