Evolutionary history of Podarcis tiliguerta on Corsica and Sardinia.

BACKGROUND: Podarcis tiliguerta is a wall lizard endemic to the Mediterranean islands of Corsica and Sardinia. Previous findings of high mtDNA and morphological diversity have led to the suggestion that it may represent a species complex. Here, we analysed mitochondrial and nuclear markers (mtDNA, 3110 bp; 6 nDNA loci, 3961 bp) in P. tiliguerta sampled from thirty-two localities across Corsica and Sardinia. RESULTS: We find much greater intraspecific genetic divergence than between sister species of other Mediterranean island Podarcis, i.e., between P. lilfordi and P. pityusensis. We detected three mtDNA clusters in Corsica (North, South-East and South-West) and either two or three in Sardinia (North vs. South) depending on the clustering method. Only one or two nDNA groups were identified within each main island (again, depending on the method). A Bayesian time-calibrated multispecies coalescent tree was obtained from mtDNA and provided statistical support for a Miocene origin of the species (13.87 Ma, 95% HPD: 18.30-10.77 Ma). The posterior mean divergence time for the Corsican and Sardinian lineages was 12.75 Ma ago (95% HPD: 16.94-9.04 Ma). CONCLUSION: The results support the evolutionary distinctiveness of Corsican and Sardinian populations and also indicate a lack of post-divergence migration despite periods of contact being possible. Further to this, species delimitation analyses of Corsican and Sardinian lineages provided statistical support for their recognition as distinct (sister) taxa. Our results provide new insights into the biogeography of the Mediterranean biodiversity hotspot, and contribute important findings relevant to the systematics and evolution of this speciose lizard genus.

Ecological divergence combined with ancient allopatry in lizard populations from a small volcanic island.

Population divergence and speciation are often explained by geographical isolation, but may also be possible under high gene flow due to strong ecology-related differences in selection pressures. This study combines coalescent analyses of genetic data (11 microsatellite loci and 1 Kbp of mtDNA) and ecological modelling to examine the relative contributions of isolation and ecology to incipient speciation in the scincid lizard Chalcides sexlineatus within the volcanic island of Gran Canaria. Bayesian multispecies coalescent dating of within-island genetic divergence of northern and southern populations showed correspondence with the timing of volcanic activity in the north of the island 1.5-3.0 Ma ago. Coalescent estimates of demographic changes reveal historical size increases in northern populations, consistent with expansions from a volcanic refuge. Nevertheless, ecological divergence is also supported. First, the two morphs showed non-equivalence of ecological niches and species distribution modelling associated the northern morph with mesic habitat types and the southern morph with xeric habitat types. It seems likely that the colour morphs are associated with different antipredator strategies in the different habitats. Second, coalescent estimation of gene copy migration (based on microsatellites and mtDNA) suggest high rates from northern to southern morphs demonstrating the strength of ecology-mediated selection pressures that maintain the divergent southern morph. Together, these findings underline the complexity of the speciation process by providing evidence for the combined effects of ecological divergence and ancient divergence in allopatry.

Multilocus genetic diversity and historical biogeography of the endemic wall lizard from Ibiza and Formentera, Podarcis pityusensis (Squamata: Lacertidae).

Two monophyletic sister species of wall lizards inhabit the two main groups of Balearic Islands: Podarcis lilfordi from islets and small islands around Mallorca and Menorca and Podarcis pityusensis from Ibiza, Formentera and associated islets. Genetic diversity within the endangered P. lilfordi has been well characterized, but P. pityusensis has not been studied in depth. Here, 2430 bp of mtDNA and 15 microsatellite loci were analysed from P. pityusensis populations from across its natural range. Two main genetic groupings were identified, although geographical structuring differed slightly between the mtDNA and the nuclear loci. In general, individuals from islets/islands adjacent to the main island of Ibiza were genetically distinct from those from Formentera and the associated Freus islands for both mtDNA and the nuclear loci. However, most individuals from the island of Ibiza were grouped with neighbouring islets/islands for nuclear loci, but with Formentera and Freus islands for the mitochondrial locus. A time-calibrated Bayesian tree was constructed for the principal mitochondrial lineages within the Balearics, using the multispecies coalescent model, and provided statistical support for divergence of the two main P. pityusensis lineages 0.111-0.295 Ma. This suggests a mid-late Pleistocene intraspecific divergence, compared with an early Pleistocene divergence in P. lilfordi, and postdates some major increases in sea level between 0.4 and 0.6 Ma, which may have flooded Formentera. The program IMa2 provided a posterior divergence time of 0.089-0.221 Ma, which was similar to the multispecies coalescent tree estimate. More significantly, it indicated low but asymmetric effective gene copy migration rates, with higher migration from Formentera to Ibiza populations. Our findings suggest that much of the present-day diversity may have originated from a late Pleistocene colonization of one island group from the other, followed by allopatric divergence of these populations. Subsequent gene flow between these insular groups seems likely to be explained by recent human introductions. Two evolutionary significant units can be defined for P. pityusensis but these units would need to exclude the populations that have been the subjects of recent admixture.

Species history and divergence times of viviparous and oviparous Chinese toad-headed sand lizards (Phrynocephalus) on the Qinghai-Tibetan Plateau.

The Qinghai-Tibetan Plateau (QTP) is an important biogeographical area and has recently become a focus for biodiversity studies. Phyrnocephalus lizards form a widespread Eurasian group with oviparous and viviparous reproductive modes, but two previous mtDNA studies of species from around the QTP have provided different phylogenetic hypotheses. We analysed three loci (mtDNA, RAG-1, AME) from all recognised Chinese Phrynocephalus species to reconstruct the speciation history of the group and to estimate species divergence times. The effects of mtDNA partitioning strategy on phylogenetic inference were examined. Bayes factor comparisons of marginal likelihoods (mLs) estimated using stepping-stone sampling revealed that partitioning strategy had a major impact on mL. Nevertheless, it had a negligible effect on the inferred tree topology. The impact of hard-bound uniform or equivalent soft-bound gamma speciation time calibration priors as well as the use of a fixed topology (as opposed to integration over all possible species histories) on divergence time estimation were also assessed, and found to have little impact on posterior estimates. All three gene trees and the species tree supported the hypothesis that the Chinese species form oviparous and viviparous sister clades. This was in agreement with an early mtDNA study but differed from a subsequent reanalysis of the mtDNA data. Inclusion of mtDNA from more widely distributed Phrynocephalus (from previous studies) indicates that the oviparous P. interscapularis from Central Asia lies outside the clade of Chinese viviparous and oviparous species, but that other Asian oviparous species lie within the Chinese oviparous clade. The median of the posterior on the divergence time of Chinese oviparous and viviparous species was 9.7 Ma ago (95% interval: 7.2-13.0 Ma ago), which coincides with major uplifting of the QTP and indicates that viviparity evolved when this clade became restricted to regions of high elevation. We also found that cladogenesis within the viviparous clade began around 5 Ma ago whereas those in the oviparous clade began around 8.6 Ma ago. We establish more robust estimates of divergence times and relationships within this important group and so provide improved insights into the origins of Phrynocephalus diversity across the QTP.

Effects of a yoga breath intervention alone and in combination with an exposure therapy for post-traumatic stress disorder and depression in survivors of the 2004 South-East Asia tsunami.

OBJECTIVE: This study evaluated the effect of a yoga breath program alone and followed by a trauma reduction exposure technique on post-traumatic stress disorder and depression in survivors of the 2004 Asian tsunami. METHOD: In this non-randomized study, 183 tsunami survivors who scored 50 or above on the Post-traumatic Checklist-17 (PCL-17) were assigned by camps to one of three groups: yoga breath intervention, yoga breath intervention followed by 3-8 h of trauma reduction exposure technique or 6-week wait list. Measures for post-traumatic stress disorder (PCL-17) and depression (BDI-21) were performed at baseline and at 6, 12 and 24 weeks. Data were analyzed using anova and mixed effects regression. RESULTS: The effect of treatment vs. control was significant at 6 weeks (F(2,178) = 279.616, P < 0.001): mean PCL-17 declined by 42.5 +/- 10.0 SD with yoga breath, 39.2 +/- 17.2 with Yoga breath + exposure and 4.6 +/- 13.2 in the control. CONCLUSION: Yoga breath-based interventions may help relieve psychological distress following mass disasters.

Age-related differences in susceptibility to cisplatin-induced renal toxicity.

Limited experimental models exist to assess drug toxicity in pediatric populations. We recently reported how a multi-age rat model could be used for pre-clinical studies of comparative drug toxicity in pediatric populations. The objective of this study was to expand the utility of this animal model, which previously demonstrated an age-dependent sensitivity to the classic nephrotoxic compound, gentamicin, to another nephrotoxicant, namely cisplatin (Cis). Sprague-Dawley rats (10, 25, 40 and 80 days old) were injected with a single dose of Cis (0, 1, 3 or 6 mg kg(-1) i.p.). Urine samples were collected prior and up to 72 h after treatment in animals that were >or= 25 days old. Several serum, urinary and 'omic' injury biomarkers as well as renal histopathology lesions were evaluated. Statistically significant changes were noted with different injury biomarkers in different age groups. The order of age-related Cis-induced nephrotoxicity was different than our previous study with gentamicin: 80 > 40 > 10 > 25 day-old vs 10 >or= 80 > 40 > 25-day-old rats, respectively. The increased levels of kidney injury molecule-1 (Kim-1: urinary protein/tissue mRNA) provided evidence of early Cis-induced nephrotoxicity in the most sensitive age group (80 days old). Levels of Kim-1 tissue mRNA and urinary protein were significantly correlated to each other and to the severity of renal histopathology lesions. These data indicate that the multi-age rat model can be used to demonstrate different age-related sensitivities to renal injury using mechanistically distinct nephrotoxicants, which is reflected in measurements of a variety of metabolite, gene transcript and protein biomarkers.

Recent volcanism and mitochondrial DNA structuring in the lizard Gallotia atlantica from the island of Lanzarote.

The phylogeography of the lacertid lizard Gallotia atlantica from the small volcanic island of Lanzarote (Canary Islands) was analysed based on 1075 bp of mitochondrial DNA (mtDNA) sequence (partial cytochrome b and ND2) for 157 individuals from 27 sites (including three sites from neighbouring islets). Levels of sequence divergence were generally low, with the most distant haplotypes separated by only 14 mutational steps. MtDNA divergence appears to coincide with formation of the middle Pleistocene lowland that united formerly separate ancient islands to form the current island of Lanzarote, allowing rejection of a two-island model of phylogeographical structure. There was evidence of large-scale population expansion after island unification, consistent with the colonization of new areas. A nested clade phylogeographical analysis (NCPA) revealed significant phylogeographical structuring. Two-step and higher-level clades each had disjunct distributions, being found to the east and west of a common area with a north-south orientation that extends between coasts in the centre-east of the island (El Jable). Other clades were almost entirely restricted to the El Jable region alone. Bayesian Markov chain Monte Carlo analyses were used to separate ongoing gene flow from historical associations. These supported the NCPA by indicating recent (75,000-150,000 years ago) east-west vicariance across the El Jable region. Lava flows covered El Jable and other parts of the central lowland at this time and likely led to population extinctions and temporary dispersal barriers, although present-day evidence suggests some populations would have survived in small refugia. Expansion of the latter appears to explain the presence of a clade located between the eastern and western components of the disjunct clades. Direct relationships between mtDNA lineages and morphology were not found, although one of two morphological forms on the island has a disjunct distribution that is broadly concordant with east-west components of the phylogeographical pattern. This work demonstrates how recent volcanic activity can cause population fragmentation and thus shape genetic diversity on microgeographical scales.

Bayesian estimation of post-Messinian divergence times in Balearic Island lizards.

Phylogenetic relationships and timings of major cladogenesis events are investigated in the Balearic Island lizards Podarcislilfordi and P.pityusensis using 2675bp of mitochondrial and nuclear DNA sequences. Partitioned Bayesian and Maximum Parsimony analyses provided a well-resolved phylogeny with high node-support values. Bayesian MCMC estimation of node dates was investigated by comparing means of posterior distributions from different subsets of the sequence against the most robust analysis which used multiple partitions and allowed for rate heterogeneity among branches under a rate-drift model. Evolutionary rates were systematically underestimated and thus divergence times overestimated when sequences containing lower numbers of variable sites were used (based on ingroup node constraints). The following analyses allowed the best recovery of node times under the constant-rate (i.e., perfect clock) model: (i) all cytochrome b sequence (partitioned by codon position), (ii) cytochrome b (codon position 3 alone), (iii) NADH dehydrogenase (subunits 1 and 2; partitioned by codon position), (iv) cytochrome b and NADH dehydrogenase sequence together (six gene-codon partitions), (v) all unpartitioned sequence, (vi) a full multipartition analysis (nine partitions). Of these, only (iv) and (vi) performed well under the rate-drift model. These findings have significant implications for dating of recent divergence times in other taxa. The earliest P.lilfordi cladogenesis event (divergence of Menorcan populations), occurred before the end of the Pliocene, some 2.6Ma. Subsequent events led to a West Mallorcan lineage (2.0Ma ago), followed 1.2Ma ago by divergence of populations from the southern part of the Cabrera archipelago from a widely-distributed group from north Cabrera, northern and southern Mallorcan islets. Divergence within P.pityusensis is more recent with the main Ibiza and Formentera clades sharing a common ancestor at about 1.0Ma ago. Climatic and sea level changes are likely to have initiated cladogenesis, with lineages making secondary contact during periodic landbridge formation. This oscillating cross-archipelago pattern in which ancient divergence is followed by repeated contact resembles that seen between East-West refugia populations from mainland Europe.

Aggregation of ampholine on heparin and other acidic polysaccharides in isoelectric focusing.

The mechanism of complexation of pI range 3.5--5 Ampholine to heparin in isoelectric focusing has been explored by the dye-binding technique at different pH values in solution. There is no significant interaction between heparin and Ampholine at pH 6.7. Weak, or selective, binding occurs at pH 5.1, and very strong interaction at pH 3.5. In the latter system, the Ampholine components appear to behave as polycations due to their ordered sequence of positive charges, each two methylene groups apart, which favors a strong binding to polyanions. In addition, there appear to be variable stoichiometries for the strong binding between heparin and Ampholine, depending on their relative amounts. It is proposed that at a low ratio of heparin to Ampholine (Ampholine excess), aggregation is perpendicular to the heparin chain, with the end ammonium charge of each Ampholine molecule neutralizing one negative charge along the heparin molecule; at higher ratios (heparin excess), the bound Ampholine segment is aligned parallel to the heparin molecule, so that on the average one Ampholine component neutralizes approx. three negative charges. The banding of heparin in isoelectric focusing in the pH range 3.0--4.5 can be explained by aggregation of the various components on heparin in amounts dependent upon the net charge on the Ampholine species at the given pH, and upon the changing stoichiometries as a function of the variation in ratio of heparin to Ampholine along the pH gradient. Binding of Ampholine to polygalacturonate was also demonstrated in excess Ampholine in a pH range dependent on the degree of protonation of the carboxyl groups of this acidic polysaccharide as well as on the net positive charge of the Ampholine. The aggregation seen at pH 4.2--4.5 led to the prediction and subsequent demonstration that polygalacturonate would also exhibit binding upon isoelectric focusing. This supports the hypothesis that aggregation of Ampholine on polyanions having sufficient charge density is a general phenomenon which can lead to spurious banding of certain polymers at appropriate pH ranges in isoelectric focusing. On the basis of their behavior in isoelectric focusing at pH 3.0--4.5, strength of aggregation of the polyanions studied appears to be heparin A = heparin B greather than polyglutamate greater than carboxyl-reduced heparin B greater than polygalacturonic acid.

Blunted beta-adrenergic responsivity of peripheral blood mononuclear cells in endogenous depression. Isoproterenol dose-response studies.

Previous studies of peripheral blood mononuclear cells isolated from drug-free, hospitalized patients with endogenous major depression have demonstrated a diminished adenosine 3',5'-monophosphate (cyclic AMP) response to single concentrations of isoproterenol as compared with that obtained from normal control subjects. We now report results of isoproterenol dose-response studies that indicate lower basal levels of cyclic AMP as well as diminished cyclic AMP levels in response to isoproterenol stimulation at concentrations ranging from 10(-10) to 10(-5) mol/L in drug-free, hospitalized patients with endogenous depression. The major factor responsible for the diminished cyclic AMP production in the depressed patients was a loss of receptor sites capable of cyclic AMP production. Taken together with our previously reported finding that beta-adrenergic antagonist binding was normal in peripheral blood mononuclear cells obtained from depressed patients, the results of the dose-response studies suggest a loss of receptor function (desensitization) rather than a diminished number of receptor binding sites (down-regulation) as the underlying mechanism. Potential explanations for beta-adrenergic desensitization and its implications for the catecholamine hypothesis of depressive disorders are discussed.

Normalization of blunted lymphocyte beta-adrenergic responsivity in melancholic inpatients by a course of electroconvulsive therapy.

Electroconvulsive therapy has been reported to desensitize brain beta-adrenergic receptors in rodents, but this effect has not been studied in man. We examined the effect of a course of electroconvulsive therapy on lymphocyte beta-adrenergic responsivity in 19 inpatients with melancholia. Before treatment, beta-adrenergic cyclic adenosine monophosphate response to isoproterenol was significantly blunted in the patients compared with controls. Following a course of electroconvulsive therapy, beta-adrenergic responsivity increased such that patients no longer differed from controls. Thus, blunted lymphocyte beta-adrenergic responsivity is a state-dependent effect of melancholia that can be corrected by a therapeutic course of electroconvulsive therapy. The effect of electroconvulsive therapy on this beta-adrenergic system is in the opposite direction to that reported for rodent forebrain, where electroconvulsive therapy causes desensitization, and may reflect differences between peripheral and central effects, species differences, or disease effects.

Regional cerebral blood flow in mood disorders. I. Comparison of major depressives and normal controls at rest.

We measured regional cerebral blood flow with the xenon 133 inhalation technique in 41 patients with major depressive disorder and 40 matched, normal controls during an eyes-closed, resting condition. The depressed group had a marked reduction in global cortical blood flow. To examine topographic abnormalities, traditional multivariate analyses were applied, as well as a new scaled subprofile model developed to identify abnormal functional neural networks in clinical samples. Both approaches indicated that the depressed sample had an abnormality in topographic distribution of blood flow, in addition to the global deficit. The scaled subprofile model identified the topographic abnormality as being due to flow reduction in the depressed patients in selective frontal, central, superior temporal, and anterior parietal regions. This pattern may reflect dysfunction in the parallel distributed cortical network involving frontal and temporoparietal polymodal association areas. The extent of this topographic abnormality, as revealed by the scaled subprofile model, was associated with both patient age and severity of depressive symptoms.

Relationship between central and peripheral serotonin indexes in depressed and suicidal psychiatric inpatients.

Serious suicidal behavior, affective disorders, and a variety of other psychopathologic behaviors and syndromes have been found to correlate with measures of the serotonin system. Clinical studies have employed a range of serotonin indexes, including the cerebrospinal fluid level of 5-hydroxyindoleacetic acid, the prolactin response to serotonin agonists, such as fenfluramine hydrochloride, and platelet serotonin-related proteins or serotonin content. Many of these indexes are correlated with suicidal behavior, but the interrelationship of these biologic measures has been uncertain. We studied the relationship of a series of serotonin indexes in patients in whom these measures were correlated with suicidal behavior. A positive correlation was found between cerebrospinal fluid 5-hydroxyindoleacetic acid and the maximal prolactin response to fenfluramine but not with platelet serotonin2 receptor indexes. The fenfluramine-stimulated maximal prolactin response correlated with platelet serotonin2 receptor number, particularly in older patients. We conclude that cerebrospinal fluid 5-hydroxyindoleacetic acid measurements cannot be replaced but can be complemented by less invasive procedures, such as a fenfluramine challenge test or platelet serotonin2 measures, in the study of the relationship of the serotonin system to psychiatric disorders.

A controlled study of the antidepressant efficacy and side effects of (-)-deprenyl. A selective monoamine oxidase inhibitor.

Monoamine oxidase (MAO) inhibitors are effective antidepressants whose use is limited because of unwanted side effects and the possibility of a tyramine-induced hypertensive crisis (cheese reaction). (-)-Deprenyl (the official nonproprietary name for this substance is selegiline), a selective MAO type B inhibitor, may be safer and have fewer side effects, but its antidepressant efficacy is uncertain. A double-blind placebo-controlled study was carried out in depressed outpatients who were treated with (-)-deprenyl in an MAO type B selective dose range and at a higher nonselective dose range. (-)-Deprenyl did not have a statistically significant antidepressant effect after three weeks of treatment at doses of 10 mg/d. However, after six weeks and at higher doses (averaging about 30 mg/d for the second three weeks), (-)-deprenyl was superior to placebo in antidepressant effect with a positive response rate of 50% vs 13.6% and with a 41% reduction in the Hamilton Depression Rating Scale mean score vs 10% in the placebo-treated group. No hypertensive crises were seen. The rate of occurrence of side effects with (-)-deprenyl was no greater than with placebo. It was concluded that (-)-deprenyl is an effective antidepressant in a dose range where it is distinguished by the absence of many of the side effects typical of nonselective MAO inhibitors.

Delusional depression and inappropriate antidiuretic hormone secretion.

Two cases of delusional major depression associated with the syndrome of inappropriate antidiuretic hormone secretion (SIADH) are described. Delusional depression and SIADH may both result from alterations of brain catecholamine neurotransmitters, and may coexist more commonly than previously thought. Implications for clinical practice and future research are discussed.

The relationship of platelet 5-HT2 receptor indices to major depressive disorder, personality traits, and suicidal behavior.

Previous research has suggested that major depression and suicidal behavior may be associated with altered serotonin receptor function. In this study, platelet serotonin2 (5-HT2) receptor binding indices were measured in conjunction with serotonin-amplified platelet aggregation, a response mediated by the platelet 5-HT2 receptor complex, in depressed patients and normal controls. The magnitude of serotonin-amplified platelet aggregation was positively correlated with the number of platelet 5-HT2 receptor sites in both groups. Mean values for the receptor binding indices and the receptor-mediated response did not differ significantly between patients and controls, although patients exhibited a wider range of values for each parameter compared with controls. Exploratory analyses were undertaken to determine clinical variables that might contribute to the increased variance in depressed individuals. These analyses failed to reveal a statistically significant relationship between any of the platelet 5-HT2 receptor measures and the subtype or severity of depressive illness, or the presence of comorbid borderline personality disorder. Although the mean number of receptor sites did not differ between patients who had recently attempted suicide and those who had never attempted suicide, a strong positive correlation (p = 0.002) was found between receptor number and the degree of medical damage resulting from the suicidal act. Furthermore, the ratio of the serotonin-amplified platelet aggregation response to platelet 5-HT2 receptor number, an index of the mean responsivity of an individual receptor complex, was lower in suicide attempters versus nonattempters (p = 0.06) and normal controls (p = 0.01). Exploratory analyses also suggested that recent exposure to psychotropic medication may result in a significant increase in platelet 5-HT2 receptor number (p = 0.03). Thus, although the study did not show a consistent alteration in platelet 5-HT2 receptor indices in major depression, the data suggest that specific factors such as suicidality and drug exposure may explain some of the variance in depressed patients.

Subsensitivity of adenylyl cyclase-coupled receptors on mononuclear leukocytes from drug-free inpatients with a major depressive episode.

Previous studies have demonstrated blunted beta-adrenergic responsivity in leukocytes from depressed patients. We sought to determine if this blunted cyclic adenosine monophosphate (AMP) response is specific for beta-adrenergic receptors (homologous), or whether other adenylyl cyclase-coupled receptors are also involved (heterologous), in order to localize this effect at the level of the receptor versus the coupling protein or the transducer, adenylyl cyclase. We studied adenylyl cyclase-mediated responses in peripheral blood mononuclear cells from 95 drug-free patients with a major depressive episode and 69 healthy controls. We found a similar degree of decrease in the peak cyclic AMP response to activation of the beta-adrenergic receptor (28%) and the prostaglandin receptor (34%) in the depressed patients, which indicated heterologous desensitization. Forskolin cyclic AMP responses were not blunted. Blunting of cyclic AMP responses to isoproterenol did not appear to correlate with levels of plasma norepinephrine and epinephrine or hypothalamic-pituitary-adrenocortical function. The absence of a decrease in the peak forskolin-generated cyclic AMP response, which involves direct activation of adenylyl cyclase, suggests an abnormality at the level of the coupling protein in these adenylyl-coupled receptors in depressed patients. Future studies need to determine whether this leukocyte signal transduction defect in depression also involves brain adenylyl cyclase-coupled receptors.

Involutional melancholia revisited.

In this study, 31 patients with involutional-onset major depression had significantly more somatization and hypochondriasis and less loss of libido, guilt, suicidal intent, and family history of depression than 60 patients with an earlier onset. Regardless of age at onset, patients over age 50 had more agitation, initial insomnia, and hypochondriasis than those under 50. These findings suggest that clinical characteristics of patients with unipolar endogenous depression may be influenced by age at both onset and time of current episode. Although there is insufficient evidence to view involutional melancholia as a separate clinical entity, further research into the genetic and biochemical basis of late-onset depression is warranted.

Interepisode consistency of dexamethasone suppression test results in affective disorders.

Twenty-two patients with recurrent affective disorders received 1-mg dexamethasone suppression tests (DSTs) during multiple hospitalizations. Interepisode consistency of DST results was found in 82% of the subjects, which supports the use of this test as a predictor of relapse.

CSF 5-HIAA and HVA concentrations in elderly depressed patients who attempted suicide.

CSF findings distinguished 12 elderly depressed patients who attempted suicide from nine depressed patients who did not and from seven normal control subjects. Psychosocial factors and measures of psychopathology did not differentiate suicidal from nonsuicidal patients. Biochemical factors may be important in evaluating suicide risk in the elderly.